@article {pmid41618386,
year = {2026},
author = {Omranikhoo, H and Rezaee, M and Verdizadeh, A and Goudarzi, Z and Jafari, M and Gholami, A and Poursadeghfard, M and Keshavarz, K},
title = {Cost-utility analysis of Edaravone compared to Riluzole in patients with amyotrophic lateral sclerosis (ALS) in Iran.},
journal = {Cost effectiveness and resource allocation : C/E},
volume = {24},
number = {1},
pages = {},
pmid = {41618386},
issn = {1478-7547},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating disease that damages motor neurons. Currently, two drugs, Riluzole and Edaravone, have been shown to slow the progression of this condition. This study aimed to evaluate the cost-utility of Edaravone compared to Riluzole in ALS patients.

METHODS: This is an economic evaluation and cost-utility analysis from Iran’s health system perspective using a 10-year and 20-year Markov model. Cost data were collected from medical records and expert interviews, while clinical outcomes and transition probabilities were obtained from a clinical trial study. The robustness of the findings was tested through both deterministic and probabilistic sensitivity analysis. Data was analyzed using Excel 2019 and TreeAge Pro 2020 software.

RESULTS: The findings of this study indicated that the cost of treatment and QALYs obtained from Edaravone (58,077 PPP$ and 1.66) compared to Riluzole (53,216 PPP$ and 1.37) were estimated to be higher in Iran. The calculated ICUR was equal to 16,704 PPP$ which is considered to be a cost-effective option in terms of the cost-effectiveness threshold to treat the patients with ALS. Furthermore, a one-way sensitivity analysis showed that the model is most affected by the cost discount rate and the price of Edaravone. Edaravone was identified as the best treatment strategy in 66% of simulations, making it the preferred option across different willingness to pay scenarios.

CONCLUSION: The findings of the study indicated that the Edaravone may be a more cost-effective and affordable option compared to the Riluzole. Consequently, the availability of this drug in the country is likely to improve the quality of life and increase the survival rates of patients.},
}

@article {pmid42414029,
year = {2026},
author = {Hata, T and Ogawa, N and Yabata, H and Kobashi, S and Nakayama, M and Ishigaki, H and Yamakawa, I and Itoh, Y and Nishino, I and Urushitani, M},
title = {Case of concurrent ALS and human T-cell leukaemia virus type 1-associated myositis.},
journal = {BMJ case reports},
volume = {19},
number = {7},
pages = {},
doi = {10.1136/bcr-2025-270944},
pmid = {42414029},
issn = {1757-790X},
abstract = {A woman in her late 70s presented with progressive limb weakness, muscle atrophy and hyper-reflexia. Laboratory findings revealed elevated creatine kinase and positive serum human T-cell leukaemia virus type 1 (HTLV-1) antibody. Clinical and electrophysiological findings met revised El Escorial criteria for amyotrophic lateral sclerosis (ALS), but muscle MRI showed inflammatory changes. Muscle biopsy revealed both neurogenic and inflammatory features. While methylprednisolone showed no benefit, intravenous immunoglobulin therapy produced transient improvement in weakness with normalisation of creatine kinase levels. The patient died from respiratory failure 3 years after symptom onset. Autopsy confirmed typical ALS-TDP pathology with phosphorylated TDP-43 inclusions in motor neurons. HTLV-1 Tax-positive lymphocytes infiltrated skeletal muscles but not the central nervous system, establishing dual pathology of ALS-TDP with HTLV-1-associated myositis. The improvement most likely reflected treatment of the HTLV-1-associated myositis rather than the underlying motor neuron disease. This case highlights the importance of evaluating treatable conditions in HTLV-1-seropositive ALS patients.},
}

@article {pmid42414791,
year = {2026},
author = {Gray, C and Hou, CG and Brayton, CE and Shepardson, RL and Leung, LB},
title = {Optimization of Virtual and In-Person Care Coordination Between VA Primary Care and Mental Health Teams: A Qualitative Study.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-026-10617-x},
pmid = {42414791},
issn = {1525-1497},
support = {I01 HX003635/HX/HSRD VA/United States ; I21 HX003593/HX/HSRD VA/United States ; IK2 HX002867/HX/HSRD VA/United States ; },
abstract = {BACKGROUND: In the Veterans Health Administration (VA), primary care teams include embedded specialists to facilitate timely access to effective mental health treatments, including same-day warm handoffs from primary care clinicians/staff to integrated mental health specialists.

OBJECTIVE: Understand the impact of the post-COVID-19 shift to virtual care on depression assessment and treatment and explore clinician-identified ways to optimize hybrid (virtual/in-person) integrated care for primary care patients with depression.

DESIGN: Semi-structured interviews across three geographically diverse VA healthcare systems.

PARTICIPANTS: Forty-seven primary care clinicians/staff and integrated mental health specialists.

APPROACH: Interview questions were based on Fortney et al.'s Reconceptualized (Digital) Access Framework. Transcripts were coded using a qualitative descriptive approach with constant comparison.

KEY RESULTS: Participants indicated that post-pandemic use of virtual care helped increase access to depression treatment. Particularly, they cited a model where integrated mental health clinicians/staff cover clinics across a healthcare system by offering telephone or video visits to patients at multiple sites. Primary care and mental health coordination appeared to work well; nevertheless, some primary care clinicians/staff preferred in-person warm handoffs. When asked about the optimal mix of in-person and virtual depression care, primary care clinicians/staff thought the initial assessment should be done in person, especially for patients presenting complicated cases. Ongoing care, namely cognitive behavioral therapy and medication management, was thought to be ideal for virtual delivery. Participants emphasized the need for offering Veteran-centric care, or care that "meets the Veterans where they are" and encourages them to continue engagement in mental healthcare.

CONCLUSIONS: Clinicians generally deferred to patients on their preferred care modality, but some indicated certain situations (e.g., initial assessment, complicated cases) may be better suited for in-person over virtual care. Further research should examine quality of virtual and in-person primary care-based mental healthcare, and patient satisfaction and experiences with these care modalities.},
}

@article {pmid42414949,
year = {2026},
author = {Njohjam, MN and Ngoule, MO and Niakam, TF},
title = {Biological sex differences in neurodegenerative diseases in Africa: a scoping review of evidence and research gaps.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-05123-w},
pmid = {42414949},
issn = {1471-2377},
abstract = {BACKGROUND: Biological sex is a well-established determinant of risk, progression, and therapeutic response in neurodegenerative diseases (NDs). However, current evidence on sex differences in NDs is from high-income Western populations. This review aims to map and synthesize evidence on biological sex differences in NDs in Africa, and to identify key research gaps.

METHODS: This scoping review was conducted in accordance with the Joanna Briggs Institute methodology and reported in accordance with the PRISMA-ScR guidelines. A literature search was conducted on PubMed, African Journals Online, Sabinet Journals, ScienceDirect, and Google Scholar. We included studies conducted in African countries that reported sex disaggregated data or examined biological sex differences in at least one ND. Data were synthesized descriptively.

RESULTS: All included studies reported sex distribution, but most (about 84%) did so only descriptively. Approximately 17% conducted sex-stratified analyses beyond prevalence. Similar to global epidemiological trends, several studies suggested a higher prevalence or odds of dementia and multiple sclerosis among females, while male predominance was observed in Parkinson's disease and Amyotrophic lateral sclerosis studies. An earlier onset and a higher mutation frequency in LRRK2-G2019S were reported in females with Parkinson's disease in some studies, while another study reported a higher mortality rate in females with dementia. No study evaluated sex specific biomarker profiles, disease progression, or treatment response.

CONCLUSIONS: Evidence on biological sex differences in NDs in Africa remains limited and is largely descriptive. Mechanistic, longitudinal, and biomarker-based investigations are largely absent.},
}

@article {pmid39821843,
year = {2025},
author = {Zhang, J and Guo, R and Zhou, Z and Fu, Z and Akogo, HY and Li, Y and Zhang, X and Wang, N and Liu, Y and Li, H and Feng, B and Cui, H and Ma, J},
title = {Neural Stem/Progenitor Cell Therapy in Patients and Animals with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.},
journal = {Molecular neurobiology},
volume = {62},
number = {5},
pages = {6521-6536},
pmid = {39821843},
issn = {1559-1182},
support = {81801278//National Natural Science Foundation of China/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Animals ; Humans ; *Neural Stem Cells/transplantation/cytology ; *Stem Cell Transplantation/methods ; Disease Models, Animal ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative malady that causes progressive degeneration and loss of motor neuron function in the brain and spinal cord, eventually resulting in muscular atrophy, paralysis, and death. Neural stem/progenitor cell (NSPC) transplantation can improve bodily function in animals and delay disease progression in patients with ALS. This paper summarizes and analyzes the efficacy and safety of neural stem/progenitor cell (NSPC) transplantation as a treatment for ALS, aiming to improve function and delay disease progression in patients. We present a summary of the pathogenic mechanism and causative genes associated with ALS and describe the mechanism and efficacy of NSPC treatment for ALS. We comprehensively searched for relevant English-language articles published between January 1, 2000 and October 1, 2023, across the following five medical databases: PubMed, EMBASE, OVID, Web of Science, and the Cochrane Library. We examined experimental indices of physical function in animals and patients who underwent stem cell transplantation. All statistical analyses were performed via Review Manager 5.4. The study comprised a total of 16 investigations, including 5 clinical studies and 11 animal studies and involving 66 patients and 203 animals. The meta-analysis revealed that the administration of NSPCs appeared to yield positive outcomes in clinical patients, as assessed by the ALS functional rating scale and forced vital capacity. Furthermore, improvements following cell injection were observed in the rotarod test results, the Basso-Beattie-Bresnahan Locomotor Rating Scale score, weight, and survival time. Our meta-analysis, which was grounded in randomized controlled trials, revealed that the transplantation of neural stem/progenitor cells (NSPCs), has potential effects on ALS patients, enhancing the physical function of animals and mitigating degenerative effects in individuals. These underscored the promise of NSPC therapy as a viable treatment option. We report that the transplantation of neural stem/progenitor cells (NSPCs) is promising for enhancing bodily function and slowing the progression of ALS in affected patients. In this review, we summarize the treatment of ALS with NSPCs, evaluating both its efficacy and safety. Through database searches, we identified 16 studies involving 66 patients and 203 animals and analyzed the experimental indices of physical function following stem cell transplantation. The meta-analysis results indicated a positive impact of NSPCs on the clinical conditions of patients and the behavior of animals. A meta-analysis of randomized controlled trials further supported the conclusion that NSPC transplantation has a beneficial effect on improving physical function and mitigating degeneration in ALS patients.},
}

*Amyotrophic Lateral Sclerosis/therapy/physiopathology
Animals
Humans
*Neural Stem Cells/transplantation/cytology
*Stem Cell Transplantation/methods
Disease Models, Animal

@article {pmid39824655,
year = {2025},
author = {Jia, M and Li, P and Yan, Y and Liu, X and Gao, L and Zhu, G and Chen, Z},
title = {Antimicrobial susceptibility and genomic characterization of Vibrio cholerae non-O1/non-O139 isolated from clinical and environmental samples in Jiaxing City, China.},
journal = {FEMS microbiology letters},
volume = {372},
number = {},
pages = {},
doi = {10.1093/femsle/fnaf009},
pmid = {39824655},
issn = {1574-6968},
support = {2024KY1697//Medical Science and Technology Project of Zhejiang Province/ ; 2023AY31028//Science and Technology Bureau of Jiaxing City/ ; },
mesh = {China ; Humans ; *Anti-Bacterial Agents/pharmacology ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; *Vibrio cholerae non-O1/genetics/drug effects/isolation & purification/pathogenicity/classification ; Drug Resistance, Bacterial/genetics ; Virulence/genetics ; Environmental Microbiology ; Virulence Factors/genetics ; Genome, Bacterial ; Genetic Variation ; },
abstract = {Non-O1/non-O139 (NOVC) strains inhabit aquatic environments and sporadically induce human illnesses. This study involved the virulence and antimicrobial genetic characterization of 176 NOVC strains, comprising 25 from clinical samples and 151 from environmental sources, collected between 2021 and 2023. The antimicrobial susceptibility of the examined NOVC population was predominantly high, exhibiting only poor susceptibility to colistin, with 89.2% resistance. The examination of virulence genes revealed that the majority of strains were positive for glucose metabolism (als gene) (169/176, 96.0%). Through multilocus sequence typing, the 176 NOVC strains were categorised into 121 sequence types, 79 of which were novel. NOVC strains demonstrate significant genetic variability and frequently engage in recombination. This work offers genetic characterization of the pathogenicity and antimicrobial resistance of a NOVC community. Our findings offer insights that may aid in the development of preventative and treatment methods for this pathogen.},
}

China
Humans
*Anti-Bacterial Agents/pharmacology
Microbial Sensitivity Tests
Multilocus Sequence Typing
*Vibrio cholerae non-O1/genetics/drug effects/isolation & purification/pathogenicity/classification
Drug Resistance, Bacterial/genetics
Virulence/genetics
Environmental Microbiology
Virulence Factors/genetics
Genome, Bacterial
Genetic Variation

@article {pmid39828018,
year = {2025},
author = {Sharma, D and Singh, V and Kumar, A and Singh, TG},
title = {Genistein: A promising ally in combating neurodegenerative disorders.},
journal = {European journal of pharmacology},
volume = {991},
number = {},
pages = {177273},
doi = {10.1016/j.ejphar.2025.177273},
pmid = {39828018},
issn = {1879-0712},
mesh = {*Genistein/therapeutic use/pharmacology ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; },
abstract = {Neurodegenerative disorders arise when nerve cells in the brain or peripheral nervous system gradually lose functions and eventually die. Although certain therapies may alleviate some of the physical and mental symptoms associated with neurodegenerative disorders, hence slowing their progression, but no sure-shot treatment is currently available. It was shown that the rise in life expectancy and the number of elderly people in the community led to an increasing trend in the incidence and prevalence of neurodegenerative disease. Phytomolecules are demonstrating their effectiveness in combating, regression, and delaying various diseases. Genistein is one of soy isoflavone with antioxidant, anti-inflammatory, and estrogenic effects. Researchers demonstrated that Genistein treatment significantly reduced hyperglycemia, improved cognitive performance by modulating acetylcholinesterase activity and oxidative stress, and alleviated neuroinflammatory conditions in mice. This paper evaluates (in vivo and in vitro) various molecular targets of isoflavones and their ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. In this review, we aim to provide an overview of the role that genistein plays in delaying the development of neurodegenerative disorders.},
}

*Genistein/therapeutic use/pharmacology
Humans
Animals
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use/pharmacology

@article {pmid39831022,
year = {2025},
author = {Okpete, UE and Byeon, H},
title = {Brain-derived neurotrophic factor alterations and cognitive decline in schizophrenia: Implications for early intervention.},
journal = {World journal of psychiatry},
volume = {15},
number = {1},
pages = {102131},
pmid = {39831022},
issn = {2220-3206},
abstract = {This manuscript explores the recent study by Cui et al which assessed the interplay between inflammatory cytokines and brain-derived neurotrophic factor (BDNF) levels in first-episode schizophrenia patients. The study revealed that higher levels of interleukin-6 and tumor necrosis factor-α correlated with reduced BDNF levels and poorer cognitive performance. Schizophrenia is a severe psychiatric disorder impacting approximately 1% of the global population, characterized by positive symptoms (hallucinations and delusions), negative symptoms (diminished motivation and cognitive impairments) and disorganized thoughts and behaviors. Emerging research highlights the role of BDNF as a potential biomarker for early diagnosis and therapeutic targeting. The findings from Cui et al's study suggest that targeting neuroinflammation and enhancing BDNF levels may improve cognitive outcomes. Effective treatment approaches involve a combination of pharmacological and non-pharmacological interventions tailored to individual patient needs. Hence, monitoring cognitive and neuroinflammatory markers is essential for improving patient outcomes and quality of life. Consequently, this manuscript highlights the need for an integrated approach to schizophrenia management, considering both clinical symptoms and underlying neurobiological changes.},
}

@article {pmid39833536,
year = {2025},
author = {Curtis, TJ and Chant, C and Quek, S and Giarenis, I and Gray, TG},
title = {Fistulae Secondary to Vaginal Pessary Use for Pelvic Organ Prolapse: A Systematic Review.},
journal = {International urogynecology journal},
volume = {36},
number = {3},
pages = {491-521},
pmid = {39833536},
issn = {1433-3023},
mesh = {Humans ; *Pessaries/adverse effects ; Female ; *Pelvic Organ Prolapse/therapy ; Risk Factors ; *Rectovaginal Fistula/etiology/epidemiology ; Retrospective Studies ; Prevalence ; },
abstract = {INTRODUCTION AND HYPOTHESIS: Urogenital and rectovaginal fistulae are rare complications of pessary use for pelvic organ prolapse (POP). This systematic review investigates the prevalence of these complications in patients using pessary for POP, potential risk factors and approaches to their investigation and management.

METHODS: All studies in English reporting urogenital or rectovaginal fistulae secondary to pessaries for POP were eligible for inclusion. AMED, CINAHL, MedLine, Scopus and Web of Science databases were searched from inception to March 2024. Risk of bias was assessed using validated tools: Murad et al.'s tool for case series/reports and ROBINS-I for non-randomised studies. Quantitative synthesis of descriptive statistics and narrative summary were performed.

RESULTS: Two retrospective studies and 60 case series/reports were included, describing 76 fistulae (34 urogenital, 42 rectovaginal). The retrospective studies estimated the prevalence of fistulae to be 3%. Of reported fistulae, 45% occurred with Gellhorn, 16% with ring, 11% with shelf and 9% with cube pessaries. Fifty percent were associated with neglected pessary care. Conservative management resulted in size reduction or resolution in 69% of fistulae: this approach should be considered. Vaginal (88%) and abdominal (100%) vesicovaginal fistula repairs were successful. Diverting ostomies were popular for rectovaginal fistulae but often resulted in permanent stoma without reducing mortality, recurrence or repair failure. Colpocleisis represents an effective procedure for managing co-existing POP.

CONCLUSIONS: The prevalence of fistulae from pessary use is likely < 1% but may rise to 3% with risk factors present, including Gellhorn pessaries and neglected care. Both conservative and surgical management are viable treatment options.},
}

Humans
*Pessaries/adverse effects
Female
*Pelvic Organ Prolapse/therapy
Risk Factors
*Rectovaginal Fistula/etiology/epidemiology
Retrospective Studies
Prevalence

@article {pmid39835009,
year = {2024},
author = {Frolov, A and D'sa, E and Henderson, C and Guzman, MA and Hayat, G and Martin, JR},
title = {Complex Genetic Framework in Familial Amyotrophic Lateral Sclerosis With a C9ORF72 Mutation: A Case Report.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e76027},
pmid = {39835009},
issn = {2168-8184},
abstract = {A significantly diverse clinical presentation of amyotrophic lateral sclerosis (ALS), even in its best-studied familial form, continues to hinder current efforts to develop effective disease-modifying drugs for the cure of this rapidly progressive, fatal neuromuscular disease. We have previously shown that clinical heterogeneity of sporadic ALS (sALS) could be explained, at least in part, by its polygenic nature as well as by the presence of mutated genes linked to non-ALS neurological diseases and genes known to mediate ALS-related pathologies. We hypothesized that a similar genetic framework could also be present in patients with familial ALS (fALS). To test this hypothesis, we conducted post-mortem genetic screening of an individual with fALS and a mutation in the C9ORF72 gene. C9ORF72 mutations are highly penetrant and are present in the majority of fALS patients. Genetic screening by whole exome sequencing (WES) on the next generation sequencing (NGS) Illumina platform (San Diego, CA, USA) followed by examination of the respective rare (minor allele frequency (MAF) ≤ 0.01) pathological/deleterious genetic variants yielded results consistent with our hypothesis of the presence of a complex genetic framework in fALS. Additional members of this genetic framework were identified when the low-frequency (0.01 < MAF < 0.05) pathological/deleterious genetic variants were analyzed with the low-frequency biallelic AHNAK2, GLI3, PTIRM1, and ZNF254 variants, warranting a closer look at their potentially important role in fALS as C9ORF72 genetic modifiers as well as their link to both neuromuscular disorders/ALS and cancer. Therefore, in addition to the current genetic screening using a standard panel of ALS-related genes, a supplementary screening by WES could be very beneficial for the development of personalized treatment of ALS patients as well as in search of the respective efficient disease-modifying drugs.},
}

@article {pmid39835561,
year = {2025},
author = {Rai, A and Shukla, S and Gupta, RK and Mishra, A},
title = {ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy.},
journal = {Current pharmaceutical design},
volume = {31},
number = {17},
pages = {1328-1346},
pmid = {39835561},
issn = {1873-4286},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Motor Neurons/drug effects/pathology ; *Medicine, Chinese Traditional ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease characterized by motor symptoms, and cognitive impairment. The complexity in treating ALS arises from genetic and environmental factors, contributing to the gradual decline of lower and upper motor neurons. The anticipated pharmaceutical market valuation for ALS is projected to reach $1,038.94 million by 2032. This projection underscores the escalating impact of ALS on global healthcare systems. ALS prevalence is expected to surge to 376,674 cases by 2040. In 2022, India ranked among the top 3 Asian-Pacific nations, while North America dominated the global ALS market. Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Drugs, Chinese Herbal/therapeutic use/pharmacology
*Neuroprotective Agents/therapeutic use/pharmacology
*Motor Neurons/drug effects/pathology
*Medicine, Chinese Traditional
Animals

@article {pmid39836043,
year = {2025},
author = {Berry, JD and Hagan, M and Zhang, J and Liu, Y and Ciepielewska, M},
title = {Longer disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis.},
journal = {Journal of comparative effectiveness research},
volume = {14},
number = {2},
pages = {e240007},
pmid = {39836043},
issn = {2042-6313},
mesh = {Humans ; *Edaravone/administration & dosage/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Retrospective Studies ; Middle Aged ; Disease Progression ; Aged ; Administration, Intravenous ; *Free Radical Scavengers/therapeutic use/administration & dosage ; },
abstract = {Aim: To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava[®] IV, Mitsubishi Tanabe Pharma America [MTPA], hereafter "IV edaravone") in a real-world setting. Background: IV edaravone is US FDA approved for the treatment of ALS and was shown in clinical trials to slow the rate of physical functional decline. Patients & methods: This retrospective observational analysis included PALS continuously enrolled in Optum's Clinformatics[®] Data Mart between 8 August 2017 and 31 December 2021. Cases treated with IV edaravone and controls not treated with IV edaravone were propensity score matched for: age, sex, race, US region of residence, pre-index disease duration, insurance, riluzole prescription; and pre-index claims for cardiovascular disease, artificial nutrition/gastrostomy tube, noninvasive ventilation and all-cause hospitalization. The index date was the first IV edaravone claim for cases; for controls, the index date was randomly assigned after IV edaravone market availability. Restricted mean time lost was calculated for the following disease progression milestones: new use of canes/walkers/wheelchairs, artificial nutrition, noninvasive ventilation, invasive ventilation, speech-generating devices and hospice. Results: Cases (n = 395) were matched to controls (n = 395). Cases had less restricted mean time lost, indicating longer disease progression milestone-free time, for all disease progression milestones. From 0 to 24 months post index, more cases (n = 129) than controls (n = 103) reported no milestones and more controls (n = 232) than cases (n = 131) reported deaths. Conclusion: In a US-based real-world setting, IV edaravone-treated PALS had a longer time to disease progression milestone events and fewer deaths in 2 years compared with PALS not treated with IV edaravone.},
}

Humans
*Edaravone/administration & dosage/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy
Male
Female
Retrospective Studies
Middle Aged
Disease Progression
Aged
Administration, Intravenous
*Free Radical Scavengers/therapeutic use/administration & dosage

@article {pmid39838927,
year = {2025},
author = {Wang, Z and Sun, Y and Bai, Z and Li, M and Kong, D and Wu, G},
title = {Mitochondria-Related Genome-Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {40},
number = {4},
pages = {693-703},
doi = {10.1002/mds.30123},
pmid = {39838927},
issn = {1531-8257},
support = {SDQLQN2021-01//Qilu Young Scholars Program of Shandong University/ ; 202306352//Taishan Scholar Foundation of Shandong Province/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; *Mitochondria/genetics/metabolism ; *Genetic Predisposition to Disease/genetics ; Quantitative Trait Loci/genetics ; },
abstract = {BACKGROUND: Mitochondrial dysfunction is increasingly recognized as a key factor in neurodegenerative diseases (NDDs), underscoring the therapeutic potential of targeting mitochondria-related genes. This study aimed to identify novel biomarkers and drug targets for these diseases through a comprehensive analysis that integrated genome-wide Mendelian randomization (MR) with genes associated with mitochondrial function.

METHODS: Using existing publicly available genome-wide association studies (GWAS) summary statistics and comprehensive data on 1136 mitochondria-related genes, we initially identified a subset of genes related to mitochondrial function that exhibited significant associations with NDDs. We then conducted colocalization and summary-data-based Mendelian randomization (SMR) analyses using expression quantitative trait loci (eQTL) to validate the causal role of these candidate genes. Additionally, we assessed the druggability of the encoded proteins to prioritize potential therapeutic targets for further exploration.

RESULTS: Genetically predicted levels of 10 genes were found to be significantly associated with the risk of NDDs. Elevated DMPK and LACTB2 levels were associated with increased Alzheimer's disease risk. Higher expression of NDUFAF2, BCKDK, and MALSU1, along with lower TTC19, raised Parkinson's disease risk. Higher ACLY levels were associated with both amyotrophic lateral sclerosis and multiple sclerosis (MS) risks, while decreased MCL1, TOP3A, and VWA8 levels raised MS risk. These genes primarily impact mitochondrial function and energy metabolism. Notably, several druggable protein targets identified are being explored for potential NDDs treatment.

CONCLUSIONS: This data-driven MR study demonstrated the causal role of mitochondrial dysfunction in NDDs. Additionally, this study identified candidate genes that could serve as potential pharmacological targets for the prevention and treatment of NDDs. © 2025 International Parkinson and Movement Disorder Society.},
}

Humans
*Mendelian Randomization Analysis
Genome-Wide Association Study
*Neurodegenerative Diseases/genetics
*Mitochondria/genetics/metabolism
*Genetic Predisposition to Disease/genetics
Quantitative Trait Loci/genetics

@article {pmid39839897,
year = {2025},
author = {Jiang, QR and Zeng, DW},
title = {Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt: Mechanistic and clinical implications.},
journal = {World journal of gastroenterology},
volume = {31},
number = {3},
pages = {100752},
pmid = {39839897},
issn = {2219-2840},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Hypertension, Portal/microbiology/surgery/virology/etiology ; *Portasystemic Shunt, Transjugular Intrahepatic/adverse effects ; *Hepatic Encephalopathy/microbiology/etiology/diagnosis ; *Liver Cirrhosis/virology/microbiology/surgery ; Hepatitis B virus/pathogenicity ; *Hepatitis B/complications ; Dysbiosis ; },
abstract = {In this article, we provide commentary on the recent article by Zhao et al. We focus on the shifts in the gut microbiota of patients with hepatitis B virus (HBV)-associated cirrhosis/portal hypertension (PH) following transjugular intrahepatic portosystemic shunt (TIPS) and the implications for understanding the mechanisms, diagnosis, and treatment. By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy, the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS, with Morganella species present only in the hepatic encephalopathy group. The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies. Furthermore, the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBV-related PH. Despite these promising findings, future studies are needed to address limitations, including a small sample size, a relatively short evaluation period for gut microbiota alterations, the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels, and the lack of validation in animal models. In conclusion, Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy, potentially through the intricate gut-liver axis, and has important clinical implications for improving the management of patients with HBV-related PH.},
}

Humans
*Gastrointestinal Microbiome
*Hypertension, Portal/microbiology/surgery/virology/etiology
*Portasystemic Shunt, Transjugular Intrahepatic/adverse effects
*Hepatic Encephalopathy/microbiology/etiology/diagnosis
*Liver Cirrhosis/virology/microbiology/surgery
Hepatitis B virus/pathogenicity
*Hepatitis B/complications
Dysbiosis

@article {pmid39842248,
year = {2025},
author = {Micallef, C and Somanadhan, S and O'Donnell, D and Thompson, W and Stokes, D and Koe, S and Davies, C},
title = {Distraction-based interventions for children in the emergency care setting: A realist synthesis based on primary research.},
journal = {Journal of pediatric nursing},
volume = {81},
number = {},
pages = {43-54},
doi = {10.1016/j.pedn.2025.01.017},
pmid = {39842248},
issn = {1532-8449},
mesh = {Humans ; Child ; *Pain Management/methods ; *Emergency Service, Hospital ; *Anxiety/prevention & control/therapy ; Male ; Female ; *Stress, Psychological/prevention & control ; Child, Preschool ; },
abstract = {BACKGROUND: The literature underscores the prevalence of pain as the most common presenting symptom in the Emergency Care Setting (ECS) and is associated with anxiety and stress for children. On top of that painful procedures are often required as part of their treatment, making procedural pain a common experience. The substantial evidence supporting the effectiveness of distraction-based interventions (DBI) in relieving pain and anxiety and reducing stress underscores the urgency of addressing this issue. However, the fragmented adoption of standardised DBI highlights the need for further research and implementation.

PURPOSE: To conduct a realist synthesis based on primary research exploring "what works for whom under what circumstances, how and why?" when implementing DBI in the ECS.

REVIEW METHODS: Empirical research evidence was retrieved systematically from eight databases covering health and social sciences. The studies were synthesised based on the principles of realist science, drawing on Pawson and Tilley's (1997) and Dalkin et al.'s (2015) programme theory development, which explains the contexts and mechanisms that generate positive outcomes about DBI for children in the ECS.

RESULTS: Of the 2099 studies screened, 64 were included. Screening was conducted 2023 to December 2024. A synthesis of the findings generated five Programme Theories (PT). PT1 focuses on the personalisation of DBI for children in the ECS, PT2 explains the importance of parental participation, PT3 highlights the importance of healthcare workers (HCWs) commitment to adopting DBI in practice, PT4 draws attention to policy-level efforts necessary for implementation support, and PT5 focuses on engaging all stakeholders in the implementation process.

CONCLUSION: To the authors' knowledge, this is the first study to apply a realist lens to understand the use of DBI in children attending the ECS and present the mechanisms that enable and/or inhibit its implementation and utilisation in everyday clinical practice.

IMPLICATIONS TO PRACTICE: This realist synthesis provides methodological guidance in the form of PT that can be utilised by clinical practitioners to adopt and implement DBI within the healthcare setting.},
}

Humans
Child
*Pain Management/methods
*Emergency Service, Hospital
*Anxiety/prevention & control/therapy
Male
Female
*Stress, Psychological/prevention & control
Child, Preschool

@article {pmid39845577,
year = {2025},
author = {Ludolph, A and Wiesenfarth, M},
title = {Tofersen and other antisense oligonucleotides in ALS.},
journal = {Therapeutic advances in neurological disorders},
volume = {18},
number = {},
pages = {17562864251313915},
pmid = {39845577},
issn = {1756-2856},
abstract = {The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?},
}

@article {pmid39854930,
year = {2025},
author = {Drouet, C and Priou, P and Gagnadoux, F and Trzepizur, W},
title = {Constraints to the initiation of home non-invasive ventilation and short-term efficacy in different diagnostic groups (as a prelude to an ambulatory shift).},
journal = {Respiratory medicine and research},
volume = {87},
number = {},
pages = {101154},
doi = {10.1016/j.resmer.2025.101154},
pmid = {39854930},
issn = {2590-0412},
mesh = {Humans ; *Noninvasive Ventilation/methods/statistics & numerical data ; Retrospective Studies ; Male ; Female ; Aged ; Middle Aged ; Cross-Sectional Studies ; *Respiratory Insufficiency/therapy/etiology ; Longitudinal Studies ; Pulmonary Disease, Chronic Obstructive/complications/therapy ; Treatment Outcome ; *Home Care Services ; Obesity Hypoventilation Syndrome/complications ; Amyotrophic Lateral Sclerosis/complications ; *Ambulatory Care ; },
abstract = {INTRODUCTION: Non-invasive ventilation (NIV) is the reference treatment for chronic respiratory failure (CRF) due to impairment of the ventilatory system. Home initiation is increasingly practiced. To better support this ambulatory shift, we aimed to assess the implementation constraints and short-term efficacy according to different aetiologies of CRF.

METHODS: This retrospective study with cross-sectional and longitudinal analysis included patients initiated with NIV at Angers University Hospital. Patients were separated according to the following aetiologies: obesity hypoventilation syndrome (OHS), chronic obstruction pulmonary disease (COPD), amyotrophic lateral sclerosis (ALS), myopathy and chest wall disease. Implementation constraints were assessed by analysing the variability of NIV settings, the number of masks tried and the duration of hospitalisation. NIV effectiveness was assessed by measuring residual PaCO2 (arterial pressure in CO2), apnoea hypopnea index (AHIflow) and tidal volume (VT) (as displayed by the NIV software).

RESULTS: Between October 2020 and May 2022, 102 patients were started with NIV, including a majority of ALS patients. We found a moderate variability in NIV settings (pressure, slope, triggers, etc.) within the different etiological groups, particularly in ALS. On the other hand, ALS patients required more interface trials than other groups and often had unmet efficacy criteria at hospital discharge. Interestingly, longitudinal follow-up showed a progressive improvement in efficacy criteria, particularly in patients who were initially inadequately ventilated.

CONCLUSION: Each aetiological group has specific constraints in the initiation of NIV that should be considered when initiating NIV in the outpatient setting.},
}

Humans
*Noninvasive Ventilation/methods/statistics & numerical data
Retrospective Studies
Male
Female
Aged
Middle Aged
Cross-Sectional Studies
*Respiratory Insufficiency/therapy/etiology
Longitudinal Studies
Pulmonary Disease, Chronic Obstructive/complications/therapy
Treatment Outcome
*Home Care Services
Obesity Hypoventilation Syndrome/complications
Amyotrophic Lateral Sclerosis/complications
*Ambulatory Care

@article {pmid39855275,
year = {2025},
author = {Zhang, W and Zhang, L and Fu, S and Yan, R and Zhang, X and Song, J and Lu, Y},
title = {Roles of NLRC4 inflammasome in neurological disorders: Mechanisms, implications, and therapeutic potential.},
journal = {Pharmacology & therapeutics},
volume = {267},
number = {},
pages = {108803},
doi = {10.1016/j.pharmthera.2025.108803},
pmid = {39855275},
issn = {1879-016X},
mesh = {Humans ; *Inflammasomes/metabolism/immunology ; Animals ; *Calcium-Binding Proteins/metabolism ; *Nervous System Diseases/drug therapy/immunology/metabolism ; *CARD Signaling Adaptor Proteins/metabolism ; *Apoptosis Regulatory Proteins/metabolism ; Neurodegenerative Diseases/drug therapy/immunology ; },
abstract = {The nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 4 (NLRC4) inflammasome, a vital component of the innate immune system, is known for defending against bacterial infections. However, recent insights have revealed its significant impact on neurological disorders. This comprehensive review discussed the mechanisms underlying the activation and regulation of the NLRC4 inflammasome, highlighting the complexity of its response to cellular stress and damage signals. The biological functions of NLRC4 were explored, particularly its influence on cytokine production and the induction of pyroptosis, a form of inflammatory cell death. This review further emphasized the role of the NLRC4 inflammasome in brain injuries and neurodegenerative disorders. In the realm of brain injuries such as stroke and traumatic brain injury, as well as in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, the NLRC4 inflammasome played a pivotal role in modulating neuroinflammatory responses, which was crucial for understanding the progression and potential therapeutic targeting of these conditions. The emerging role of NLRC4 in psychiatric disorders and its potential impact on glioma progression were also examined. Additionally, this review presented a thorough summary of the latest research on inhibitors that impeded the assembly and activation of the NLRC4 inflammasome, pointing to new therapeutic possibilities in neurological disorders. In conclusion, by integrating current knowledge on the activation and regulation of NLRC4 with its biological functions and clinical implications, this article underscored the importance of NLRC4 inflammasome in neurological pathologies, which opened new possibilities for the treatment of challenging neurological conditions.},
}

Humans
*Inflammasomes/metabolism/immunology
Animals
*Calcium-Binding Proteins/metabolism
*Nervous System Diseases/drug therapy/immunology/metabolism
*CARD Signaling Adaptor Proteins/metabolism
*Apoptosis Regulatory Proteins/metabolism
Neurodegenerative Diseases/drug therapy/immunology

@article {pmid39857620,
year = {2024},
author = {Frawley, L and Taylor, NT and Sivills, O and McPhillamy, E and To, TD and Wu, Y and Chin, BY and Wong, CY},
title = {Stem Cell Therapy for the Treatment of Amyotrophic Lateral Sclerosis: Comparison of the Efficacy of Mesenchymal Stem Cells, Neural Stem Cells, and Induced Pluripotent Stem Cells.},
journal = {Biomedicines},
volume = {13},
number = {1},
pages = {},
pmid = {39857620},
issn = {2227-9059},
support = {Australian Government New Colombo Plan (NCP) scheme//Australian Government New Colombo Plan (NCP) scheme/ ; },
abstract = {BACKGROUND/OBJECTIVES: Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a debilitating, incurable neurodegenerative disorder characterised by motor neuron death in the spinal cord, brainstem, and motor cortex. With an incidence rate of about 4.42 cases per 100,000 people annually, ALS severely impacts motor function and quality of life, causing progressive muscle atrophy, spasticity, paralysis, and eventually death. The cause of ALS is largely unknown, with 90% of cases being sporadic and 10% familial. Current research targets molecular mechanisms of inflammation, excitotoxicity, aggregation-prone proteins, and proteinopathy.

METHODS: This review evaluates the efficacy of three stem cell types in ALS treatment: mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs).

RESULTS: MSCs, derived from various tissues, show neuroprotective and regenerative qualities, with clinical trials suggesting potential benefits but limited by small sample sizes and non-randomised designs. NSCs, isolated from the fetal spinal cord or brain, demonstrate promise in animal models but face functional integration and ethical challenges. iPSCs, created by reprogramming patient-specific somatic cells, offer a novel approach by potentially replacing or supporting neurons. iPSC therapy addresses ethical issues related to embryonic stem cells but encounters challenges regarding genotoxicity and epigenetic irregularities, somatic cell sources, privacy concerns, the need for extensive clinical trials, and high reprogramming costs.

CONCLUSIONS: This research is significant for advancing ALS treatment beyond symptomatic relief and modest survival extensions to actively modifying disease progression and improving patient outcomes. Successful stem cell therapies could lead to new ALS treatments, slowing motor function loss and reducing symptom severity.},
}

@article {pmid39857761,
year = {2025},
author = {Sun, C and Chen, Y and Xu, L and Wang, W and Zhang, N and Fournier, CN and Li, N and Fan, D},
title = {Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale as a Novel Tool to Measure Disease Progression.},
journal = {Biomedicines},
volume = {13},
number = {1},
pages = {},
pmid = {39857761},
issn = {2227-9059},
support = {82001347//National Natural Science Foundation of China/ ; 82071426//National Natural Science Foundation of China/ ; 81701067//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; },
abstract = {Background: A valuable outcome measure to monitor amyotrophic lateral sclerosis (ALS) disease progression is crucial in clinical trials. Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) is a novel questionnaire assessing ALS disability. Currently, there are no studies on the relationship between ROADS and ALS survival. This study explored the value of Chinese ROADS as a novel tool for measuring disease progression and the correlation between ROADS and ALS survival. Methods: A total of 170 ALS participants were included in this study. Clinical characteristics and baseline ROADS, ΔROADS, ALSFRS-R, and ΔFRS of patients were collected. Participants were followed for 18 months to assess time to tracheostomy and survival. Scales were collected every 3 to 6 months. We evaluated the association of baseline ROADS and ΔROADS with survival using Cox regression analyses. Linear mixed effects models were used to assess changes over time in ROADS and ALSFRS-R. Results: Multivariate Cox models confirmed that baseline ROADS positively correlated with ALS survival (HR = 0.95, p < 0.001), while baseline ΔROADS negatively correlated with survival (HR = 1.26, p < 0.001). Additionally, linear mixed effects models suggested that ROADS, similar to ALSFRS-R, declined significantly over time, but there was no significant difference between these two. Conclusions: Our study indicates that Chinese ROADS is strongly related to ALS survival. Changes in ROADS with disease progression are similar to those in ALSFRS-R. These findings support Chinese ROADS as a reliable outcome measure for clinical trials, potentially enhancing the dimension of evaluating treatment effectiveness in ALS trials.},
}

@article {pmid39863029,
year = {2025},
author = {Liu, X and Li, T and Tu, X and Xu, M and Wang, J},
title = {Mitochondrial fission and fusion in neurodegenerative diseases:Ca[2+] signalling.},
journal = {Molecular and cellular neurosciences},
volume = {132},
number = {},
pages = {103992},
doi = {10.1016/j.mcn.2025.103992},
pmid = {39863029},
issn = {1095-9327},
mesh = {Humans ; *Mitochondrial Dynamics/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; *Calcium Signaling ; Animals ; *Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; },
abstract = {Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive loss of neuronal structure and function. The pathogenesis is intricate and involves a network of interactions among multiple causes and systems. Mitochondria and Ca[2+] signaling have long been considered to play important roles in the development of various NDs. Mitochondrial fission and fusion dynamics are important processes of mitochondrial quality control, ensuring the stability of mitochondrial structure and function. Mitochondrial fission and fusion imbalance and Ca[2+] signaling disorders can aggravate the disease progression of NDs. In this review, we explore the relationship between mitochondrial dynamics and Ca[2+] signaling in AD, PD, ALS, and HD, focusing on the roles of key regulatory proteins (Drp1, Fis1, Mfn1/2, and Opa1) and the association structures between mitochondria and the endoplasmic reticulum (MERCs/MAMs). We provide a detailed analysis of their involvement in the pathogenesis of these four NDs. By integrating these mechanisms, we aim to clarify their contributions to disease progression and offer insights into the development of therapeutic strategies that target mitochondrial dynamics and Ca[2+] signaling. We also examine the progress in drug research targeting these pathways, highlighting their potential as therapeutic targets in the treatment of NDs.},
}

Humans
*Mitochondrial Dynamics/physiology
*Neurodegenerative Diseases/metabolism/pathology
*Calcium Signaling
Animals
*Mitochondria/metabolism
Mitochondrial Proteins/metabolism

@article {pmid39863163,
year = {2025},
author = {Kearney, CA and Needle, CD and Brinks, AL and Gutierrez, D and Lo Sicco, KI},
title = {Response to Sood et al's "Systemic Janus kinase inhibitor treatment for vitiligo: An evidence-based review".},
journal = {Journal of the American Academy of Dermatology},
volume = {92},
number = {5},
pages = {e155-e156},
doi = {10.1016/j.jaad.2025.01.059},
pmid = {39863163},
issn = {1097-6787},
}

@article {pmid39865792,
year = {2025},
author = {Murakami, E and Shibata, T and Tomemori, M and Kawai, G and Nakatani, K},
title = {The role of spatial arrangement of aromatic rings on the binding of N,N'-diheteroaryl guanidine ligands to the G2C4/G2C4 motif DNA.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {27},
number = {6},
pages = {3341-3350},
doi = {10.1039/d4cp03213f},
pmid = {39865792},
issn = {1463-9084},
mesh = {*DNA/chemistry/metabolism ; Ligands ; Surface Plasmon Resonance ; *Guanidine/chemistry/analogs & derivatives ; Circular Dichroism ; Hydrogen Bonding ; Humans ; },
abstract = {Non-canonical DNA structures formed by aberrantly expanded repeat DNA are implicated in promoting repeat instability and the onset of repeat expansion diseases. Small molecules that target these disease-causing repeat DNAs hold promise as therapeutic agents for such diseases. Specifically, 1,3-di(quinolin-2-yl)guanidine (DQG) has been identified to bind to the disease-causing GGCCCC (G2C4) repeat DNA associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In this study, we investigate the structure-binding relationships between DQG analogs and double-stranded DNA (dsDNA) containing a G2C4/G2C4 unit. Our findings, derived from UV melting temperature, circular dichroism spectra, and surface plasmon resonance (SPR) analyses of DQG analogs, highlight the crucial role of the spatial arrangements of aromatic rings in binding to the G2C4/G2C4 unit. Among the tested DQG analogs, N,N'-di(quinazolin-2-yl)guanidine (DQzG) stands out for its ability to form seven planar conformers. These conformers enable ADD-DAA hydrogen bonding with cytosine and multiple spatial arrangements of aromatic rings, including those resembling DQG. Our binding analyses revealed that DQzG exhibits the highest affinity binding for the G2C4/G2C4 unit. NMR analysis of the DQzG-bound G2C4/G2C4-dsDNA further suggested that DQzG binds to the G2C4/G2C4 unit via hydrogen bonding. Moreover, SPR analysis demonstrated that DQzG binds more strongly to G2C4 repeat DNA compared to DQG. These results position DQzG as a promising lead compound for targeting the G2C4 repeat, offering potential therapeutic avenues for the treatment of ALS/FTD and other repeat expansion diseases.},
}

*DNA/chemistry/metabolism
Ligands
Surface Plasmon Resonance
*Guanidine/chemistry/analogs & derivatives
Circular Dichroism
Hydrogen Bonding
Humans

@article {pmid39868844,
year = {2025},
author = {Elyaman, W and Stern, LJ and Jiang, N and Dressman, D and Bradley, P and Klatzmann, D and Bradshaw, EM and Farber, DL and Kent, SC and Chizari, S and Funk, K and Devanand, D and Thakur, KT and Raj, T and Dalahmah, OA and Sarkis, RA and Weiner, HL and Shneider, NA and Przedborski, S},
title = {Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {2},
pages = {e14548},
pmid = {39868844},
issn = {1552-5279},
support = {T32 AI148099/AI/NIAID NIH HHS/United States ; P01 AI106697/AI/NIAID NIH HHS/United States ; R01AI137198/NH/NIH HHS/United States ; R13 AG090018/AG/NIA NIH HHS/United States ; R01 AG067581/AG/NIA NIH HHS/United States ; R01 AG076018/AG/NIA NIH HHS/United States ; R35 GM141457/GM/NIGMS NIH HHS/United States ; P30 AG066514/AG/NIA NIH HHS/United States ; T32AI148099-4/NH/NIH HHS/United States ; AI106697/NH/NIH HHS/United States ; R01 AG055422/AG/NIA NIH HHS/United States ; R01AG067581/NH/NIH HHS/United States ; R13AG090018-01/NH/NIH HHS/United States ; R01AG076018/NH/NIH HHS/United States ; AG R01AG055422/NH/NIH HHS/United States ; R35GM141457/NH/NIH HHS/United States ; R01 AI137198/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/immunology/therapy ; *Brain/immunology ; Immunotherapy ; *Neurodegenerative Diseases/immunology/therapy ; *T-Lymphocytes/immunology ; },
abstract = {This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases. HIGHLIGHTS: Researchers gathered to discuss approaches to study T cells in brain disorders. New technologies allow high-throughput screening of antigen-specific T cells. Microbial infections can precede several serious and chronic neurological diseases. Central and peripheral T cell responses shape neurological disease pathology. Immunotherapy can induce regulatory T cell responses in neuroinflammatory disorders.},
}

Humans
*Alzheimer Disease/immunology/therapy
*Brain/immunology
Immunotherapy
*Neurodegenerative Diseases/immunology/therapy
*T-Lymphocytes/immunology

@article {pmid39871559,
year = {2025},
author = {Rani, S and Tuteja, M},
title = {Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.},
journal = {Current protein & peptide science},
volume = {26},
number = {6},
pages = {451-466},
pmid = {39871559},
issn = {1875-5550},
mesh = {Humans ; *Molecular Chaperones/metabolism ; Animals ; Protein Folding/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy ; Heat-Shock Proteins/metabolism ; *Protein Aggregation, Pathological/drug therapy/metabolism ; Protein Aggregates/drug effects ; Molecular Targeted Therapy ; *Proteostasis Deficiencies/drug therapy/metabolism ; },
abstract = {The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.},
}

Humans
*Molecular Chaperones/metabolism
Animals
Protein Folding/drug effects
*Neurodegenerative Diseases/metabolism/drug therapy
Heat-Shock Proteins/metabolism
*Protein Aggregation, Pathological/drug therapy/metabolism
Protein Aggregates/drug effects
Molecular Targeted Therapy
*Proteostasis Deficiencies/drug therapy/metabolism

@article {pmid39871563,
year = {2025},
author = {Guo, J and Liu, XY and Yang, SS and Li, Q and Duan, Y and Zhu, SS and Zhou, K and Yan, YZ and Zeng, P},
title = {Roles of C/EBPβ/AEP in Neurodegenerative Diseases.},
journal = {Current topics in medicinal chemistry},
volume = {25},
number = {20},
pages = {2440-2452},
pmid = {39871563},
issn = {1873-4294},
support = {82301506//National Natural Science Foundation of China/ ; 220XQD090//Research Foundation of Scientific Research Program of University of South China/ ; 2023JJ40560//Provincial Natural Science Foundation of Hunan/ ; S202410555234, S202410555259, S202410555262//Science and Technology Innovation Project for College Students/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/antagonists & inhibitors/chemistry ; Animals ; Small Molecule Libraries/chemistry/pharmacology ; },
abstract = {In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.},
}

Humans
*Neurodegenerative Diseases/metabolism/drug therapy/pathology
*CCAAT-Enhancer-Binding Protein-beta/metabolism/antagonists & inhibitors/chemistry
Animals
Small Molecule Libraries/chemistry/pharmacology

@article {pmid39879320,
year = {2025},
author = {Guillot, SJ and Lang, C and Simonot, M and Beckett, D and Lulé, D and Balz, LT and Knehr, A and Stuart-Lopez, G and Vercruysse, P and Dieterlé, S and Weydt, P and Dorst, J and Kandler, K and Kassubek, J and Wassermann, L and Rouaux, C and Arthaud, S and Da Cruz, S and Luppi, PH and Roselli, F and Ludolph, AC and Dupuis, L and Bolborea, M},
title = {Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models.},
journal = {Science translational medicine},
volume = {17},
number = {783},
pages = {eadm7580},
doi = {10.1126/scitranslmed.adm7580},
pmid = {39879320},
issn = {1946-6242},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/drug therapy ; Disease Models, Animal ; Humans ; *Orexins/antagonists & inhibitors/metabolism ; Mice ; *Sleep/drug effects ; Male ; *Orexin Receptor Antagonists/therapeutic use/pharmacology ; Female ; Melanins/pharmacology/therapeutic use ; Pituitary Hormones/pharmacology/therapeutic use ; Hypothalamic Hormones/pharmacology/therapeutic use/administration & dosage ; Motor Neurons/pathology/drug effects ; Wakefulness/drug effects ; Mice, Transgenic ; Middle Aged ; *Sleep Wake Disorders/drug therapy/complications/physiopathology ; Polysomnography ; },
abstract = {Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic C9ORF72 and SOD1 mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep. Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (Sod1[G86R], Fus[ΔNLS/+], and TDP43[Q331K]). A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of Sod1[G86R] mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease.},
}

Animals
*Amyotrophic Lateral Sclerosis/physiopathology/complications/drug therapy
Disease Models, Animal
Humans
*Orexins/antagonists & inhibitors/metabolism
Mice
*Sleep/drug effects
Male
*Orexin Receptor Antagonists/therapeutic use/pharmacology
Female
Melanins/pharmacology/therapeutic use
Pituitary Hormones/pharmacology/therapeutic use
Hypothalamic Hormones/pharmacology/therapeutic use/administration & dosage
Motor Neurons/pathology/drug effects
Wakefulness/drug effects
Mice, Transgenic
Middle Aged
*Sleep Wake Disorders/drug therapy/complications/physiopathology
Polysomnography

@article {pmid39880333,
year = {2025},
author = {Izrael, M and Chebath, J and Molakandov, K and Revel, M},
title = {Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.},
journal = {Advanced drug delivery reviews},
volume = {218},
number = {},
pages = {115525},
doi = {10.1016/j.addr.2025.115525},
pmid = {39880333},
issn = {1872-8294},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Pluripotent Stem Cells/transplantation/cytology ; Animals ; *Cell- and Tissue-Based Therapy/methods ; *Stem Cell Transplantation/methods ; Clinical Trials as Topic ; },
abstract = {Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems. Over the past two decades, comprehensive preclinical efficacy (proof-of-concept) and safety studies have led to the initiation of First-in-Human phase I-II clinical trials for a range of neurodegenerative diseases. In this review, we explore the fundamentals and challenges of neural-cell therapies derived from pluripotent stem cells for treating neurodegenerative diseases. Additionally, we highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in treating neurodegenerative diseases such as spinal cord injury (SCI), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), as well as advances in retina diseases such as Stargardt disease (a.k.a fundus flavimaculatus), retinitis pigmentosa (RP) and age-related macular degeneration (AMD). These trials will pave the way for the development of new cell-based therapies targeting additional neurological conditions, including Alzheimer's disease and epilepsy.},
}

Humans
*Neurodegenerative Diseases/therapy
*Pluripotent Stem Cells/transplantation/cytology
Animals
*Cell- and Tissue-Based Therapy/methods
*Stem Cell Transplantation/methods
Clinical Trials as Topic

@article {pmid39882923,
year = {2025},
author = {Koltsova, E and Smotraiev, R and Nehrii, A and Zhekeev, M and Ratnaweera, H},
title = {Mechanisms for removing phosphorus species through sequential coagulation using inorganic coagulants and organic polymers.},
journal = {Water science and technology : a journal of the International Association on Water Pollution Research},
volume = {91},
number = {2},
pages = {202-218},
pmid = {39882923},
issn = {0273-1223},
mesh = {*Phosphorus/chemistry/isolation & purification ; *Polymers/chemistry ; *Water Pollutants, Chemical/chemistry/isolation & purification ; Alum Compounds/chemistry ; *Waste Disposal, Fluid/methods ; *Water Purification/methods ; Flocculation ; Phosphates/chemistry ; },
abstract = {The need for stringent phosphorus removal from domestic wastewater is increasing to mitigate eutrophication, while efficient phosphate reuse is critical due to the global phosphate crisis. Combining aluminum sulfate (ALS) with high molecular weight organic polymers achieved 95-99% removal of particles, turbidity, and phosphates, reducing ALS usage by 40%. We propose mechanisms to explain the enhanced treatment efficiency. Particle and turbidity removal is more influenced by polymer charge density than molecular weight, while orthophosphate (OP) removal is linked to a change in zeta potential from negative to positive, allowing additional OP binding through complex formation with hydrolysis products and polymers. Enhanced phospholipid (PL) removal likely results from adsorption and neutralization of micelle PL charges by intermediate positively charged aluminum hydroxyphosphate ions. Higher PL removal with low ALS doses is attributed to a two-stage dosing process that optimizes coagulant and polymer dosages. The combined removal of OP and PL improves phosphorus bioavailability, increasing the sludge's fertilizer value.},
}

*Phosphorus/chemistry/isolation & purification
*Polymers/chemistry
*Water Pollutants, Chemical/chemistry/isolation & purification
Alum Compounds/chemistry
*Waste Disposal, Fluid/methods
*Water Purification/methods
Flocculation
Phosphates/chemistry

@article {pmid39884579,
year = {2025},
author = {Liu, WW and Wei, JC},
title = {Response to Vera et al's "Interleukin-23 inhibition associates with lower incidence of cardiovascular risk factor type diseases compared to biologic naïve patients with psoriasis: A retrospective cohort study".},
journal = {Journal of the American Academy of Dermatology},
volume = {92},
number = {5},
pages = {e157-e158},
doi = {10.1016/j.jaad.2024.12.044},
pmid = {39884579},
issn = {1097-6787},
}

@article {pmid39891383,
year = {2025},
author = {Chen, M and Cui, H and Zhang, X and Ma, S and Guo, J and Liu, Z and Gu, D and Fan, Y},
title = {Super-Enhancer Protects Cells From Toxicity of C9orf72 Poly(proline-arginine) by Inducing the Expression of KPNA2/KPNB1.},
journal = {Cell biochemistry and function},
volume = {43},
number = {2},
pages = {e70053},
doi = {10.1002/cbf.70053},
pmid = {39891383},
issn = {1099-0844},
support = {//This work was supported by the National Natural Science Foundation of China (31970616, 82070505) and Jiangsu Provincial Natural Science Foundation (BK20211330)./ ; },
mesh = {Humans ; *alpha Karyopherins/genetics/metabolism ; *C9orf72 Protein/metabolism/genetics ; Cell Nucleus/metabolism ; Triazoles/pharmacology ; Cell Death/drug effects ; Azepines ; },
abstract = {Hexanucleotide repeat expansions in C9orf72 are the most common genetic mutation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Dipeptide repeat (DPR) proteins, such as poly(proline-arginine) (polyPR) generated from G4C2 repeat expansions, have been shown to be highly toxic. In this study, PR20 was labeled with fluorescein isothiocyanate (FITC) to track its cellular localization. Several cell lines demonstrated survival under PR20 treatment by sequestering PR20 in the cytoplasm. Treatment with JQ-1 or Ivermectin (Iver) translocated PR20 into the nucleus, leading to cell death. Mechanistically, KPNA2/KPNB1 interacted with PR20 in the cytoplasm and hindered PR20 from entering the cell nucleus. Genetic silencing of KPNA2/KPNB1 converted PR20-resistant cells into PR20-sensitive cells. Treatment with JQ1 significantly reduced the protein levels of KPNA2/KPNB1, allowing PR20 to enter the nucleus. Overexpression of KPNA2 or KPNB1 effectively blocked cell death induced by co-treatment with JQ-1 and PR20. Our results indicate that super-enhancers shield cells from PR20 toxicity by upregulating the expression of KPNA2/KPNB1.},
}

Humans
*alpha Karyopherins/genetics/metabolism
*C9orf72 Protein/metabolism/genetics
Cell Nucleus/metabolism
Triazoles/pharmacology
Cell Death/drug effects
Azepines

@article {pmid39893487,
year = {2025},
author = {Pilotto, F and Smeele, PH and Scheidegger, O and Diab, R and Schobesberger, M and Sierra-Delgado, JA and Saxena, S},
title = {Kaempferol enhances ER-mitochondria coupling and protects motor neurons from mitochondrial dysfunction and ER stress in C9ORF72-ALS.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {21},
pmid = {39893487},
issn = {2051-5960},
support = {725825//European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program/ ; },
mesh = {Animals ; *Endoplasmic Reticulum Stress/drug effects/physiology ; *Kaempferols/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/pathology/genetics/drug therapy/metabolism ; *Mitochondria/drug effects/metabolism/pathology ; Humans ; C9orf72 Protein/genetics/metabolism ; *Motor Neurons/drug effects/metabolism/pathology ; *Neuroprotective Agents/pharmacology ; Mice ; *Endoplasmic Reticulum/drug effects/metabolism ; Mice, Transgenic ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Rats ; },
abstract = {Repeat expansions in the C9ORF72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Considerable progress has been made in identifying C9ORF72-mediated disease and resolving its underlying etiopathogenesis. The contributions of intrinsic mitochondrial deficits as well as chronic endoplasmic reticulum stress to the development of the C9ORF72-linked pathology are well established. Nevertheless, to date, no cure or effective therapy is available, and thus attempts to find a potential drug target, have received increasing attention. Here, we investigated the mode of action and therapeutic effect of a naturally occurring dietary flavanol, kaempferol in preclinical rodent and human models of C9ORF72-ALS. Notably, kaempferol treatment of C9ORF72-ALS human patient-derived motor neurons/neurons, resolved mitochondrial deficits, promoted resiliency against severe ER stress, and conferred neuroprotection. Treatment of symptomatic C9ORF72 mice with kaempferol, normalized mitochondrial calcium uptake, restored mitochondria function, and diminished ER stress. Importantly, in vivo, chronic kaempferol administration ameliorated pathological motor dysfunction and inhibited motor neuron degeneration, highlighting the translational potential of kaempferol. Lastly, in silico modelling identified a novel kaempferol target and mechanistically the neuroprotective mechanism of kaempferol is through the iP3R-VDAC1 pathway via the modulation of GRP75 expression. Thus, kaempferol holds great promise for treating neurodegenerative diseases where both mitochondrial and ER dysfunction are causally linked to the pathophysiology.},
}

Animals
*Endoplasmic Reticulum Stress/drug effects/physiology
*Kaempferols/pharmacology/therapeutic use
*Amyotrophic Lateral Sclerosis/pathology/genetics/drug therapy/metabolism
*Mitochondria/drug effects/metabolism/pathology
Humans
C9orf72 Protein/genetics/metabolism
*Motor Neurons/drug effects/metabolism/pathology
*Neuroprotective Agents/pharmacology
Mice
*Endoplasmic Reticulum/drug effects/metabolism
Mice, Transgenic
Disease Models, Animal
Male
Mice, Inbred C57BL
Rats

@article {pmid39894843,
year = {2025},
author = {Chen, L and Shen, Q and Liu, Y and Zhang, Y and Sun, L and Ma, X and Song, N and Xie, J},
title = {Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.},
journal = {Signal transduction and targeted therapy},
volume = {10},
number = {1},
pages = {31},
pmid = {39894843},
issn = {2059-3635},
support = {32471049//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170984//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32200802//National Natural Science Foundation of China (National Science Foundation of China)/ ; ZR2020YQ23//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; ZR2024MC153//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; },
mesh = {Humans ; *Iron/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology/genetics ; *Homeostasis ; Zinc/metabolism ; Copper/metabolism ; Animals ; Parkinson Disease/metabolism/genetics/drug therapy/pathology ; Alzheimer Disease/metabolism/genetics/drug therapy/pathology ; Manganese/metabolism ; Oxidative Stress ; Chelating Agents/therapeutic use ; },
abstract = {As essential micronutrients, metal ions such as iron, manganese, copper, and zinc, are required for a wide range of physiological processes in the brain. However, an imbalance in metal ions, whether excessive or insufficient, is detrimental and can contribute to neuronal death through oxidative stress, ferroptosis, cuproptosis, cell senescence, or neuroinflammation. These processes have been found to be involved in the pathological mechanisms of neurodegenerative diseases. In this review, the research history and milestone events of studying metal ions, including iron, manganese, copper, and zinc in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), will be introduced. Then, the upstream regulators, downstream effector, and crosstalk of mental ions under both physiologic and pathologic conditions will be summarized. Finally, the therapeutic effects of metal ion chelators, such as clioquinol, quercetin, curcumin, coumarin, and their derivatives for the treatment of neurodegenerative diseases will be discussed. Additionally, the promising results and limitations observed in clinical trials of these metal ion chelators will also be addressed. This review will not only provide a comprehensive understanding of the role of metal ions in disease development but also offer perspectives on their modulation for the prevention or treatment of neurodegenerative diseases.},
}

Humans
*Iron/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy/pathology/genetics
*Homeostasis
Zinc/metabolism
Copper/metabolism
Animals
Parkinson Disease/metabolism/genetics/drug therapy/pathology
Alzheimer Disease/metabolism/genetics/drug therapy/pathology
Manganese/metabolism
Oxidative Stress
Chelating Agents/therapeutic use

@article {pmid39902643,
year = {2025},
author = {Abad-Yang, N and Raguseo, F and Di Michele, L and Patani, R and Di Antonio, M},
title = {The potential of multimolecular G-quadruplex structures for targeted treatment of Amyotrophic Lateral Sclerosis.},
journal = {Expert opinion on therapeutic targets},
volume = {29},
number = {1-2},
pages = {1-4},
doi = {10.1080/14728222.2025.2463361},
pmid = {39902643},
issn = {1744-7631},
}

@article {pmid39907297,
year = {2024},
author = {Čižek Sajko, M and Suklan, J and Osmanović, D and Peterlin, B},
title = {Translational Research on Polygenic Risk Scores in Common Neurodegenerative Diseases - A Scoping Review Protocol.},
journal = {Acta medica academica},
volume = {53},
number = {3},
pages = {303-308},
pmid = {39907297},
issn = {1840-2879},
mesh = {Humans ; Alzheimer Disease/genetics/diagnosis ; Amyotrophic Lateral Sclerosis/genetics ; Genetic Predisposition to Disease ; *Genetic Risk Score ; *Multifactorial Inheritance ; Multiple Sclerosis/genetics ; *Neurodegenerative Diseases/genetics ; Parkinson Disease/genetics/diagnosis ; Research Design ; Risk Assessment ; Risk Factors ; Scoping Reviews as Topic ; *Translational Research, Biomedical ; },
abstract = {OBJECTIVE: The purpose of this protocol is to clearly describe the process for the scoping review we plan to conduct on the topic of polygenic risk scores (PRS) in common neurodegenerative diseases. We will present the review's objective, the strategy for evidence search, the data extraction and analysis procedure, and how the results will be presented.

METHODS: The inclusion criteria for the planned scoping review will focus on evidence sources that involve PRS applied to neurogenerative diseases such as Multiple sclerosis, Parkinson's disease, Alzheimer's disease, and Amyotrophic lateral sclerosis in any phase of translational research, from early development to clinical implementation. This includes its use in risk prediction, early diagnosis, prognosis, and treatment decision-making. The research questions were created based on the population, context, and concept framework. We will consider both peer-reviewed papers and grey literature published in English or German for inclusion. Two independent reviewers will search for information.

CONCLUISON: The findings from the scoping review will be presented descriptively and summarized according to the research questions to illustrate the current status of translational research on PRS in common neurodegenerative diseases.},
}

Humans
Alzheimer Disease/genetics/diagnosis
Amyotrophic Lateral Sclerosis/genetics
Genetic Predisposition to Disease
*Genetic Risk Score
*Multifactorial Inheritance
Multiple Sclerosis/genetics
*Neurodegenerative Diseases/genetics
Parkinson Disease/genetics/diagnosis
Research Design
Risk Assessment
Risk Factors
Scoping Reviews as Topic
*Translational Research, Biomedical

@article {pmid39910731,
year = {2025},
author = {Singh, S and Khan, S and Khan, S and Ansari, O and Malhotra, N and Shukla, SK and Narang, J},
title = {Muscle Matters: Transforming Amyotrophic Lateral Sclerosis Diagnostics with Next-Gen Biosensors and Smart Detection.},
journal = {ACS chemical neuroscience},
volume = {16},
number = {4},
pages = {563-587},
doi = {10.1021/acschemneuro.4c00664},
pmid = {39910731},
issn = {1948-7193},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/genetics ; Humans ; *Biosensing Techniques/methods ; Biomarkers ; Electromyography/methods ; Motor Neurons ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily targets the motor system, causing patients' speech and swallowing ability to rapidly deteriorate. Although ALS is usually classified into familial and sporadic forms, diagnosing it can be extremely difficult due to the absence of definitive biomarkers, often resulting in delays in diagnosis. Current diagnostic practices rely heavily on clinical assessments that indicate damage to both upper motor neurons (UMNs) and lower motor neurons (LMNs). This includes comprehensive physical examinations, electromyography (EMG) to assess neuromuscular function, and the exclusion of other similar conditions such as cervical spondylotic myelopathy, multifocal motor neuropathy, and Kennedy's disease through appropriate diagnostic procedures. The urgent need for specific biomarkers is critical for timely diagnosis and therapeutic advancements in ALS management. While many recent developments in research have not yet translated into direct patient benefits, the recognition of ALS as a complex disease is beginning to influence clinical practice significantly. Optimal management strategies emphasize on symptom control and improving the quality of life for patients within a holistic healthcare framework. This review provides a comprehensive overview of ALS, delving into its pathophysiology, clinical symptoms, and the latest advancements in detection methods that utilize traditional approaches, innovative biosensors, and smart diagnostic technologies. It discusses various treatment options available for ALS while exploring future developments that may enhance patient screening and improve clinical outcomes. By integrating assessments into the underlying mechanisms of the disease with cutting-edge diagnostic approaches, this review aims to contribute meaningfully to ongoing efforts to optimize ALS management and therapeutic strategies, ultimately improving patient care and outcomes.},
}

*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/genetics
Humans
*Biosensing Techniques/methods
Biomarkers
Electromyography/methods
Motor Neurons

@article {pmid39924695,
year = {2025},
author = {Liu, S and Geng, D},
title = {White-Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study.},
journal = {Brain and behavior},
volume = {15},
number = {2},
pages = {e70286},
pmid = {39924695},
issn = {2162-3279},
support = {82372048//National Natural Science Foundation of China/ ; 22TS1400900//Science and Technology Commission of Shanghai Municipality/ ; 22ZR1409500//Science and Technology Commission of Shanghai Municipality/ ; 23S31904100//Science and Technology Commission of Shanghai Municipality/ ; 24SF1904200//Science and Technology Commission of Shanghai Municipality/ ; 24SF1904201//Science and Technology Commission of Shanghai Municipality/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Magnetic Resonance Imaging ; Mendelian Randomization Analysis/methods ; Neural Pathways/pathology ; *White Matter/diagnostic imaging/pathology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) and white-matter structural connectivity have been linked in some observational studies, although it is unknown if this is a causal relationship. The purpose of this study was to examine the impact of various white-matter structural connectivity on AD via a two-sample multivariate Mendelian randomization (MR) approach.

METHODS: The genome-wide association study (GWAS) of Wainberg et al. provided the summary data on white-matter structural connectivity, and Bellenguez et al.'s study provided the GWAS aggregated data for AD. MR methods included inverse variance weighted, Mendelian randomization Egger, simple mode, weighted median, and weighted mode. Heterogeneity, horizontal pleiotropy, and "leave-one-out" analysis guaranteed the robustness of causation. Finally, reverse MR analysis was conducted on the white-matter structural connectivity that showed positive results in the forward MR analysis.

RESULTS: Among 206 white-matter structural connections, we identified 10 connections were strongly correlated with genetic susceptibility to AD. Right-hemisphere limbic network to thalamus white-matter structural connectivity and Right-hemisphere salience_ventral attention network to accumbens white-matter structural connectivity were positively correlated with the likelihood of AD, while the remaining 8 white-matter structural connections were negatively related with AD. None of the above 10 white-matter structural connections have a reverse causal relationship with AD.

CONCLUSION: Our MR study reveals a certain degree of association between white-matter structural connectivity and AD, which may provide support for future diagnosis and treatment of AD.},
}

Humans
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Genetic Predisposition to Disease
Genome-Wide Association Study
Magnetic Resonance Imaging
Mendelian Randomization Analysis/methods
Neural Pathways/pathology
*White Matter/diagnostic imaging/pathology

@article {pmid39928236,
year = {2025},
author = {Kaspute, G and Ramanavicius, A and Prentice, U},
title = {Natural drug delivery systems for the treatment of neurodegenerative diseases.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {217},
pmid = {39928236},
issn = {1573-4978},
support = {S-MIP-24-111//Research Council of Lithuania (LMTLT)/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism/drug effects ; Animals ; *Biological Products/therapeutic use/administration & dosage ; Nanoparticles/chemistry ; Liposomes ; Anti-Inflammatory Agents ; Biological Availability ; },
abstract = {Today, herbal drugs are prominent in the pharmaceutical industry due to their well-known therapeutic and side effects. Plant-based compounds often face limitations such as poor solubility, low bioavailability, and instability in physiological environments, restricting their therapeutic efficacy and delivery. Nanotechnology-based solutions, including nanoparticle formulations and advanced delivery systems like liposomes and transfersomes, address these issues by enhancing solubility, stability, bioavailability, and targeted delivery, thereby optimizing the therapeutic potential of phytoactive compounds. Neuroinflammation can be a cause of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, or amyotrophic lateral sclerosis. Consequently, there is a need for the optimal delivery of a pharmacological anti-inflammatory agents to the CNS. Thus, the non-invasive administration of a stable compound at a therapeutic concentration is needed to assure molecule crossing through the blood-brain barrier. Natural resources have more structural diversity and novelty than synthetic compounds, e.g. plant-derived drug products have higher molecular weights, incorporate more oxygen atoms, and are more complex. As a result, plant-derived products have unique features which can be used to effectively modulate neuroinflammation. Therefore, this review aims to identify herbal molecules capable of targeting neuroinflammation and present novel strategies for their efficient delivery.},
}

Humans
*Neurodegenerative Diseases/drug therapy
*Drug Delivery Systems/methods
Blood-Brain Barrier/metabolism/drug effects
Animals
*Biological Products/therapeutic use/administration & dosage
Nanoparticles/chemistry
Liposomes
Anti-Inflammatory Agents
Biological Availability

@article {pmid39932195,
year = {2025},
author = {Ruggieri, V and Scaricamazza, S and Bracaglia, A and D'Ercole, C and Parisi, C and D'Angelo, P and Proietti, D and Cappelletti, C and Macone, A and Lozanoska-Ochser, B and Bouchè, M and Latella, L and Valle, C and Ferri, A and Giordani, L and Madaro, L},
title = {Polyamine metabolism dysregulation contributes to muscle fiber vulnerability in ALS.},
journal = {Cell reports},
volume = {44},
number = {1},
pages = {115123},
doi = {10.1016/j.celrep.2024.115123},
pmid = {39932195},
issn = {2211-1247},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Polyamines/metabolism ; *Muscle Fibers, Skeletal/metabolism/pathology ; Mice ; Superoxide Dismutase-1/metabolism/genetics ; Mice, Transgenic ; Disease Models, Animal ; Humans ; Motor Neurons/metabolism/pathology ; Muscle, Skeletal/metabolism/pathology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive paralysis due to motor neuron degeneration with no curative therapy despite extensive biomedical research. One of the primary targets of ALS is skeletal muscle, which undergoes profound functional changes as the disease progresses. To better understand how altered innervation interferes with muscle homeostasis during disease progression, we generated a spatial transcriptomics dataset of skeletal muscle in the SOD1[G93A] mouse model of ALS. Using this strategy, we identified polyamine metabolism as one of the main altered pathways in affected muscle fibers. By establishing a correlation between the vulnerability of muscle fibers and the dysregulation of this metabolic pathway, we show that disrupting polyamine homeostasis causes impairments similar to those seen in ALS muscle. Finally, we show that restoration of polyamine homeostasis rescues the muscle phenotype in SOD1[G93A] mice, opening new perspectives for the treatment of ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Polyamines/metabolism
*Muscle Fibers, Skeletal/metabolism/pathology
Mice
Superoxide Dismutase-1/metabolism/genetics
Mice, Transgenic
Disease Models, Animal
Humans
Motor Neurons/metabolism/pathology
Muscle, Skeletal/metabolism/pathology

@article {pmid39933302,
year = {2025},
author = {Li, H and Qiao, Z and Xiao, X and Cao, X and Li, Z and Liu, M and Jiao, Q and Chen, X and Du, X and Jiang, H},
title = {G protein-coupled receptors: A golden key to the treasure-trove of neurodegenerative diseases.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {46},
number = {},
pages = {155-168},
doi = {10.1016/j.clnu.2025.01.032},
pmid = {39933302},
issn = {1532-1983},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Animals ; },
abstract = {G protein-coupled receptors (GPCRs) are a class of transmembrane proteins that distribute in various organs extensively. They can regulate physiological functions such as perception, neurotransmission and endocrinology through the synergies of signaling pathways. At present, Food and Drug Administration (FDA) have approved more than 500 drugs targeting GPCRs to treat a variety of conditions, including neurological diseases, gastrointestinal diseases and tumors. Conformational diversity and dynamic changes make GPCRs a star target for the treatment of neurodegenerative diseases. Moreover, GPCRs can also open biased signaling pathways for G protein and β-arrestin, which has unique functional selectivity and the possibility of overcoming side effects. Some studies believe that biased drugs will be the mainstream direction of drug innovation in the future. To disclose the essential role and research process of GPCRs in neurodegenerative diseases, we firstly reviewed several pivotal GPCRs and their mediated signaling pathways in Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Then we focused on the biased signaling pathway of GPCRs in these diseases. Finally, we updated the GPCR drugs under research for the treatment of neurodegenerative diseases in the clinical trials or approval. This review could provide valuable targets for precision therapy to cope with the dysfunction of neurodegenerative diseases in the future.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
*Receptors, G-Protein-Coupled/metabolism
Signal Transduction
Animals

@article {pmid39936266,
year = {2025},
author = {Denton, TT and Carter, GT and Goddard, M and Weiss, J and Weeks, DL and Weydt, P and Russo, EB and Weiss, MD},
title = {Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications.},
journal = {Muscle & nerve},
volume = {72},
number = {1},
pages = {7-14},
doi = {10.1002/mus.28359},
pmid = {39936266},
issn = {1097-4598},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; Animals ; *Cannabinoids/therapeutic use/pharmacology ; *Endocannabinoids/metabolism/therapeutic use ; Mice ; },
abstract = {A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously. Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS. The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders. Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1 [G93A] mouse model of ALS. The use of CEs in SOD1 [G93A] murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease. Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
Humans
Animals
*Cannabinoids/therapeutic use/pharmacology
*Endocannabinoids/metabolism/therapeutic use
Mice

@article {pmid39938752,
year = {2025},
author = {Zhu, Y and Tian, M and Lu, S and Qin, Y and Zhao, T and Shi, H and Li, Z and Qin, D},
title = {The antioxidant role of aromatic plant extracts in managing neurodegenerative diseases: A comprehensive review.},
journal = {Brain research bulletin},
volume = {222},
number = {},
pages = {111253},
doi = {10.1016/j.brainresbull.2025.111253},
pmid = {39938752},
issn = {1873-2747},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Antioxidants/pharmacology/therapeutic use ; *Plant Extracts/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Animals ; Polyphenols/pharmacology/therapeutic use ; },
abstract = {Neurodegenerative diseases (NDDs) are a class of cognitive and motor disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), and others. They are caused by lesions in cells and tissues of the central nervous system, resulting in corresponding dysfunctions and consequent decline in cognitive and motor functions. Neural tissues are extremely vulnerable to oxidative stress, which plays critical biological roles in NDDs. Aromatic compounds are found extensively in natural plants and have substantial effects of anti-oxidative stress damage, which not only have a wide range of research applications in cosmetics, foods, etc., but are also frequently utilized in the treatment of various central nervous system diseases. This review summarizes the relevant oxidative stress mechanisms in NDDs (AD, PD, HD, and ALS) and reviews aromatic compounds such as polyphenols, terpenoids, and flavonoids that can be used in the management of neurodegenerative diseases, as well as their specific mechanisms of antioxidant action. This review will serve as a reference for future experimental studies on neurodegenerative illnesses while also offering fresh insights into clinical therapy.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
*Antioxidants/pharmacology/therapeutic use
*Plant Extracts/pharmacology/therapeutic use
Oxidative Stress/drug effects
Animals
Polyphenols/pharmacology/therapeutic use

@article {pmid39940644,
year = {2025},
author = {Lee, AJB and Bi, S and Ridgeway, E and Al-Hussaini, I and Deshpande, S and Krueger, A and Khatri, A and Tsui, D and Deng, J and Mitchell, CS},
title = {Restoring Homeostasis: Treating Amyotrophic Lateral Sclerosis by Resolving Dynamic Regulatory Instability.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
pmid = {39940644},
issn = {1422-0067},
support = {P30 AG066511/AG/NIA NIH HHS/United States ; R35GM152245/NH/NIH HHS/United States ; 1944247//National Science Foundation/ ; 253558//Chan Zuckerberg Initiative/ ; R35 GM152245/GM/NIGMS NIH HHS/United States ; T32 EB025816/EB/NIBIB NIH HHS/United States ; U19 AG065169/AG/NIA NIH HHS/United States ; R01 AG070937/AG/NIA NIH HHS/United States ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/therapy/genetics/pathology/drug therapy/physiopathology ; Animals ; *Homeostasis ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase-1/genetics/metabolism ; Humans ; Disease Progression ; Computer Simulation ; },
abstract = {Amyotrophic lateral sclerosis (ALS) has an interactive, multifactorial etiology that makes treatment success elusive. This study evaluates how regulatory dynamics impact disease progression and treatment. Computational models of wild-type (WT) and transgenic SOD1-G93A mouse physiology dynamics were built using the first-principles-based first-order feedback framework of dynamic meta-analysis with parameter optimization. Two in silico models were developed: a WT mouse model to simulate normal homeostasis and a SOD1-G93A ALS model to simulate ALS pathology dynamics and their response to in silico treatments. The model simulates functional molecular mechanisms for apoptosis, metal chelation, energetics, excitotoxicity, inflammation, oxidative stress, and proteomics using curated data from published SOD1-G93A mouse experiments. Temporal disease progression measures (rotarod, grip strength, body weight) were used for validation. Results illustrate that untreated SOD1-G93A ALS dynamics cannot maintain homeostasis due to a mathematical oscillating instability as determined by eigenvalue analysis. The onset and magnitude of homeostatic instability corresponded to disease onset and progression. Oscillations were associated with high feedback gain due to hypervigilant regulation. Multiple combination treatments stabilized the SOD1-G93A ALS mouse dynamics to near-normal WT homeostasis. However, treatment timing and effect size were critical to stabilization corresponding to therapeutic success. The dynamics-based approach redefines therapeutic strategies by emphasizing the restoration of homeostasis through precisely timed and stabilizing combination therapies, presenting a promising framework for application to other multifactorial neurodegenerative diseases.},
}

*Amyotrophic Lateral Sclerosis/metabolism/therapy/genetics/pathology/drug therapy/physiopathology
Animals
*Homeostasis
Mice
Mice, Transgenic
Disease Models, Animal
Superoxide Dismutase-1/genetics/metabolism
Humans
Disease Progression
Computer Simulation

@article {pmid39940966,
year = {2025},
author = {Jamerlan, AM and Shim, KH and Sharma, N and An, SSA},
title = {Multimer Detection System: A Universal Assay System for Differentiating Protein Oligomers from Monomers.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
pmid = {39940966},
issn = {1422-0067},
support = {RS-2023-00251396//National Research Foundation of Korea/ ; 2021R1A6A1A03038996//National Research Foundation of Korea/ ; },
mesh = {Humans ; alpha-Synuclein/metabolism ; *Protein Multimerization ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; *Protein Aggregation, Pathological/metabolism ; DNA-Binding Proteins/metabolism ; },
abstract = {Depositions of protein aggregates are typical pathological hallmarks of various neurodegenerative diseases (NDs). For example, amyloid-beta (Aβ) and tau aggregates are present in the brain and plasma of patients with Alzheimer's disease (AD); α-synuclein in Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA); mutant huntingtin protein (Htt) in Huntington's disease (HD); and DNA-binding protein 43 kD (TDP-43) in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). The same misfolded proteins can be present in multiple diseases in the form of mixed proteinopathies. Since there is no cure for all these diseases, understanding the mechanisms of protein aggregation becomes imperative in modern medicine, especially for developing diagnostics and therapeutics. A Multimer Detection System (MDS) was designed to distinguish and quantify the multimeric/oligomeric forms from the monomeric form of aggregated proteins. As the unique epitope of the monomer is already occupied by capturing or detecting antibodies, the aggregated proteins with multiple epitopes would be accessible to both capturing and detecting antibodies simultaneously, and signals will be generated from the oligomers rather than the monomers. Hence, MDS could present a simple solution for measuring various conformations of aggregated proteins with high sensitivity and specificity, which may help to explore diagnostic and treatment strategies for developing anti-aggregation therapeutics.},
}

Humans
alpha-Synuclein/metabolism
*Protein Multimerization
*Neurodegenerative Diseases/metabolism
Protein Aggregates
tau Proteins/metabolism
Amyloid beta-Peptides/metabolism
*Protein Aggregation, Pathological/metabolism
DNA-Binding Proteins/metabolism

@article {pmid39941101,
year = {2025},
author = {Orywal, K and Socha, K and Iwaniuk, P and Kaczyński, P and Farhan, JA and Zoń, W and Łozowicka, B and Perkowski, M and Mroczko, B},
title = {Vitamins in the Prevention and Support Therapy of Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
pmid = {39941101},
issn = {1422-0067},
support = {NdS/551580/2022/2022//Polish Ministry of Education and Science/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/drug therapy ; *Vitamins/therapeutic use/pharmacology ; Animals ; Parkinson Disease/prevention & control ; Dietary Supplements ; Neuroprotective Agents/therapeutic use ; Oxidative Stress/drug effects ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), which are a consequence of the progressive loss of neuronal function and structure, cause significant cognitive impairment. The incidence of these diseases in the world's population is constantly increasing as a result of an aging population. Although genetic and environmental factors are most often mentioned as the pathogenetic factors of these diseases, increasing evidence points to the important role of proper nutrition in the prevention and support of the treatment of these disorders. A healthy, balanced diet can mitigate the risks associated with the risk factors mentioned above and slow the progression of the disease by reducing oxidative stress and inflammation. Vitamins B, D, E, C, K, and A have been shown to support cognitive functions and protect the nervous system. This review demonstrates the importance of vitamins in preventing and supporting the therapy of neurodegenerative diseases. Information regarding the health-promoting properties of these vitamins must be effectively communicated to consumers seeking to protect their health, particularly in the context of neurodegenerative diseases. Consequently, this review also examines the authorized health claims under EU food law related to these vitamins, assessing their role in promoting awareness of the vitamins' potential benefits for neuroprotection and the management of neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/prevention & control/drug therapy
*Vitamins/therapeutic use/pharmacology
Animals
Parkinson Disease/prevention & control
Dietary Supplements
Neuroprotective Agents/therapeutic use
Oxidative Stress/drug effects

@article {pmid39945200,
year = {2025},
author = {Rovito, MJ and Martinez, S and Thomas, K and Chauhan, K and Gibson, S},
title = {Women, Men, and Cancer Survivorship: A Commentary on Current Data and Possible Underlying Issues.},
journal = {American journal of men's health},
volume = {19},
number = {1},
pages = {15579883241309039},
pmid = {39945200},
issn = {1557-9891},
mesh = {Humans ; Male ; Female ; *Cancer Survivors/statistics & numerical data ; *Neoplasms/mortality/epidemiology/diagnosis ; *Survivorship ; United States/epidemiology ; Survival Rate ; Sex Factors ; },
abstract = {Tonorezos et al.'s recent analysis of U.S. cancer survivorship prevalence provides insightful commentary on the dramatic increase of those surviving the disease over the last 50 years. This growth is reflective of improvements in cancer detection, treatment, and the effects of an aging population. While survival rates have seen a significant increase, more focus is needed on the long term and postsurvivorship health care. What Tonorezos et al.'s piece also indicates is that survivorship trends reveal disparities based on several variables, such as age, sex, and cancer type. Women tend to be diagnosed earlier and have higher survival rates when compared to men, arguably due to more frequent screenings vis-a-vis a sequela of increased utilization of care. Men have higher cancer incidence rates among the aging population, accompanied by lower survival rates, frequently linked to late diagnosis and less utilization of preventive care. Addressing sex-specific disparities is pivotal to developing future treatment plans among cancer survivors. Health care providers must adjust to the multifaceted demands of the population. Public health movements should focus on increasing awareness and promotion of early detection in the male population, taking note of the successful initiatives seen in women's health. It is imperative that these disparities and long-term needs are assimilated into the comprehensive conversation about cancer care to improve outcomes for all survivors.},
}

Humans
Male
Female
*Cancer Survivors/statistics & numerical data
*Neoplasms/mortality/epidemiology/diagnosis
*Survivorship
United States/epidemiology
Survival Rate
Sex Factors

@article {pmid39946662,
year = {2025},
author = {Cordts, I and Fuetterer, C and Wachinger, A and von Heynitz, R and Kessler, T and Freigang, M and Quinten, AL and Bjelica, B and Brakemeier, S and Hobbiebrunken, E and Hagenacker, T and Petri, S and Koch, JC and Hahn, A and Lingor, P and Deschauer, M and Günther, R and Weiler, M and Haller, B and Feneberg, E},
title = {Long-Term Dynamics of CSF and Serum Neurofilament Light Chain in Adult Patients With 5q Spinal Muscular Atrophy Treated With Nusinersen.},
journal = {Neurology},
volume = {104},
number = {5},
pages = {e213371},
pmid = {39946662},
issn = {1526-632X},
mesh = {Humans ; Female ; Male ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Adult ; Retrospective Studies ; *Oligonucleotides/therapeutic use ; Middle Aged ; *Muscular Atrophy, Spinal/drug therapy/cerebrospinal fluid/blood ; Biomarkers/cerebrospinal fluid/blood ; Young Adult ; },
abstract = {BACKGROUND AND OBJECTIVES: The availability of disease-modifying therapies for 5q-associated spinal muscular atrophy (SMA) has heightened the need to identify suitable biomarkers. This study investigates neurofilament light chain (NfL) concentrations during long-term nusinersen treatment in adult SMA.

METHODS: In a retrospective study of prospectively collected data, NfL concentrations in the CSF (cNfL) and serum (sNfL) were measured in patients with SMA from 8 German centers and in neurologic controls using a single-molecule array (Simoa) assay. NfL concentrations and clinical characteristics, including the clinical scores Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), were analyzed for defined treatment intervals (T1-T4 [loading phase until 4 months], T5-T8 [until 23 months], T9-T12 [until 37 months], and T13-T19 [until 60 months]). Linear mixed models with a random intercept were used to assess the changes in NfL levels during treatment, considering time and covariates as fixed effects.

RESULTS: One hundred thirteen adult patients with SMA (median age 35, 46% female), with a treatment duration of maximum 60 months, and 52 controls were included. At baseline, NfL concentrations were significantly higher in SMA {cNfL median, 585 (interquartile range [IQR] 428-787) pg/mL; sNfL, 11 (IQR 8-14) pg/mL}
than in controls (cNfL, 420 [IQR 323-662] pg/mL; sNfL, 8 [IQR 6-12] pg/mL) (cNfL, p = 0.021; sNfL, p = 0.030). Median differences for all clinical scores were the highest for T5-T8 compared with the loading phase (Δ HFMSE, 0.6 [IQR 0.1-1.4], p = 0.017; Δ RULM, 0.9 [IQR 0.4-1.3], p < 0.001; Δ ALSFRS-R, 0.7 [IQR 0.4-1.0], p < 0.001), but not for subsequent intervals. Longitudinal analysis revealed a significant decrease of NfL concentrations during each treatment interval compared with the loading phase (p < 0.05, respectively) except for sNfL in T13-T19. Even among patients with no measurable clinical improvement (Δ HFMSE ≤ 0), more than 50% showed declining cNfL and sNfL levels up to T13-T19.

DISCUSSION: NfL decreased during nusinersen treatment, suggesting its potential as a pharmacodynamic response marker in adult SMA. However, in patients without detectable clinical improvement, our study cannot determine whether they represent a more sensitive outcome measure or are not clinically meaningful.},
}

Humans
Female
Male
*Neurofilament Proteins/blood/cerebrospinal fluid
Adult
Retrospective Studies
*Oligonucleotides/therapeutic use
Middle Aged
*Muscular Atrophy, Spinal/drug therapy/cerebrospinal fluid/blood
Biomarkers/cerebrospinal fluid/blood
Young Adult

@article {pmid39947279,
year = {2025},
author = {Gelbenegger, G and Cheskes, S and Jilma, B and Zeitlinger, M and Lin, S and Drennan, IR and Jorda, A},
title = {Amiodarone dose in patients with shockable out-of-hospital cardiac arrest.},
journal = {Resuscitation},
volume = {209},
number = {},
pages = {110534},
doi = {10.1016/j.resuscitation.2025.110534},
pmid = {39947279},
issn = {1873-1570},
mesh = {Humans ; *Amiodarone/administration & dosage ; *Out-of-Hospital Cardiac Arrest/therapy/mortality/drug therapy ; Male ; Female ; *Anti-Arrhythmia Agents/administration & dosage ; Aged ; Middle Aged ; *Cardiopulmonary Resuscitation/methods ; Registries ; *Electric Countershock/methods ; Dose-Response Relationship, Drug ; Treatment Outcome ; },
abstract = {BACKGROUND: Amiodarone is used in shockable out-of-hospital cardiac arrest (OHCA), but the ideal dose is unknown.

METHODS: This was an analysis from the Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry (2011-2015). Patients with shockable OHCA who received 5 or more defibrillation attempts and treatment with 300 or 450 mg of amiodarone were included. Outcomes were ROSC at ED arrival, survival at hospital discharge, and favorable neurologic function at discharge. Group-differences were adjusted for using inverse probability weighting and a multiple logistic regression model.

RESULTS: The present study included 910 patients; 426 received amiodarone 300 mg and 484 received amiodarone 450 mg. The amiodarone 300 mg group had a higher estimated probability of ROSC at ED arrival as compared with the amiodarone 450 mg group (30.8% [95% CI, 26.6-35.1] vs 24.2% [95% CI, 20.5-27.9], respectively; adjusted probability difference, 6.6% (0.9-12.3), p = 0.0234). The group differences in survival at hospital discharge (21.3% [95% CI, 17.2-25.4] vs 18.0% [95% CI, 14.6-21.5]; adjusted probability difference, 3.3% [-2.3-8.8]) and favorable neurologic outcome at discharge (16.5% [95% CI, 12.9-20.2] vs 12.7% [95% CI, 9.5-16.0]; adjusted probability difference, 3.8% [95% CI, -1.2-8.7]) did not reach statistical significance.

CONCLUSION: In patients with shockable OHCA who received 5 or more defibrillation attempts, a dose of amiodarone 300 mg was associated with a similar survival compared with a total dose of amiodarone 450 mg. Further study is needed to evaluate the need for a second administration of amiodarone in patients with shockable OHCA.},
}

Humans
*Amiodarone/administration & dosage
*Out-of-Hospital Cardiac Arrest/therapy/mortality/drug therapy
Male
Female
*Anti-Arrhythmia Agents/administration & dosage
Aged
Middle Aged
*Cardiopulmonary Resuscitation/methods
Registries
*Electric Countershock/methods
Dose-Response Relationship, Drug
Treatment Outcome

@article {pmid39947630,
year = {2025},
author = {Moreno-Martinez, L and Gaja-Capdevila, N and Mosqueira-Martín, L and Herrando-Grabulosa, M and Rodriguez-Gomez, L and Gonzalez-Imaz, K and Calvo, AC and Sagartzazu-Aizpurua, M and Moreno-García, L and Fuentes, JM and Acevedo-Arozena, A and Aizpurua, JM and Miranda, JI and López de Munain, A and Vallejo-Illarramendi, A and Navarro, X and Osta, R and Gil-Bea, FJ},
title = {Novel FKBP prolyl isomerase 1A (FKBP12) ligand promotes functional improvement in SOD1[G93A] amyotrophic lateral sclerosis (ALS) mice.},
journal = {British journal of pharmacology},
volume = {182},
number = {11},
pages = {2466-2486},
doi = {10.1111/bph.17448},
pmid = {39947630},
issn = {1476-5381},
support = {PID2022-140354OB-I00//Agencia Estatal de Investigación/ ; PID2020-119780RB-100//Agencia Estatal de Investigación/ ; IKERBASQUE/PP/2022/003//Ikerbasque, Basque Foundation for Science/ ; PIF19/184//Euskal Herriko Unibertsitatea/ ; PI2020/08-1//CIBER-CALS/ ; CB06/05/1105//Instituto de Salud Carlos III of Spain/ ; CB06/05/0041//Instituto de Salud Carlos III of Spain/ ; BIO19/ROCHE/017/BD//Roche Stop Fuga de Cerebros/ ; IT1732-22//Basque Government/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/physiopathology/genetics ; Ligands ; Mice ; *Superoxide Dismutase-1/genetics ; Mice, Transgenic ; *Tacrolimus Binding Protein 1A/metabolism ; Disease Models, Animal ; Humans ; Male ; Motor Neurons/drug effects ; Ryanodine Receptor Calcium Release Channel/metabolism ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment options. ALS pathogenesis involves intricate processes within motor neurons, characterized by dysregulated Ca[2+] influx and buffering in early ALS-affected motor neurones. This study proposes the modulation of ryanodine receptors (RyRs), key mediators of intracellular Ca[2+], as a therapeutic target.

EXPERIMENTAL APPROACH: A novel class of novel FKBP12 ligands that show activity as cytosolic calcium modulators through stabilizing RyR channel activity, were tested in the superoxide dismutase 1 (SOD1)[G93A] mouse model of ALS. Different outcomes were used to assess treatment efficacy, including electrophysiology, histopathology, neuromuscular function and survival.

KEY RESULTS: Among the novel FKBP12 ligands, MP-010 was chosen for its central nervous system availability and favourable in vitro pharmaco-toxicological profile. Chronic administration of MP-010 to SOD1[G93A] mice produced preservation of motor nerve conduction, with the 61-mg·kg[-1] dose significantly delaying the onset of motor impairment. This was accompanied by improved motor coordination, increased innervated endplates and significant preservation of motor neurones in the spinal cord of treated mice. Notably, MP-010 treatment significantly extended lifespan by an average of 10 days compared to vehicle.

CONCLUSIONS AND IMPLICATIONS: FKBP12 ligands, particularly MP-010, exhibit promising neuroprotective effects in ALS, highlighting their potential as novel therapeutic agents. Further investigations into the molecular mechanisms and clinical translatability of these compounds are needed for their application in ALS treatment.},
}

Animals
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/physiopathology/genetics
Ligands
Mice
*Superoxide Dismutase-1/genetics
Mice, Transgenic
*Tacrolimus Binding Protein 1A/metabolism
Disease Models, Animal
Humans
Male
Motor Neurons/drug effects
Ryanodine Receptor Calcium Release Channel/metabolism
Mice, Inbred C57BL

@article {pmid39953725,
year = {2025},
author = {Nishida, K and Sakashita, K and Futamura, N},
title = {Decision-making trends in therapeutic interventions for multiple system atrophy: a 24-year retrospective study.},
journal = {Movement disorders clinical practice},
volume = {12},
number = {6},
pages = {823-827},
pmid = {39953725},
issn = {2330-1619},
support = {JPMH23FC1010//the Ministry of Health, Labour and Welfare, Japan/ ; },
mesh = {Humans ; *Multiple System Atrophy/therapy ; Retrospective Studies ; Male ; Female ; Middle Aged ; *Tracheostomy/trends ; Aged ; Enteral Nutrition/trends ; Japan ; Adult ; *Respiration, Artificial/trends ; *Clinical Decision-Making ; Age Factors ; },
abstract = {BACKGROUND: Managing multiple system atrophy (MSA) is challenging. While invasive interventions for amyotrophic lateral sclerosis are well-studied, those for MSA remain less explored.

OBJECTIVES: To explore factors influencing treatment choices and trends in advanced-stage MSA.

METHODS: A retrospective cohort study analyzed 128 MSA patients at Hyogo Chuo National Hospital, Japan, from 2000 to 2024, focusing on treatment period and age at onset.

RESULTS: Tracheostomy invasive ventilation (TIV) decreased after 2014 (26.9% vs. 9.2%; P = 0.023). TIV-treated patients remained similarly young before and after 2014 (age at onset 52.7 vs. 54.5 years; P = 0.659) and tracheostomy was chosen by younger patients after 2014 (58.3 vs. 51.5 years; P < 0.001). Conversely, enteral nutrition increased in older patients (57.4 vs. 62.9 years; P = 0.011).

CONCLUSIONS: In Japanese MSA, preferences for invasive treatments shifted, with younger patients favoring TIV and tracheostomy, while older patients preferred less invasive options, emphasizing personalized care.},
}

Humans
*Multiple System Atrophy/therapy
Retrospective Studies
Male
Female
Middle Aged
*Tracheostomy/trends
Aged
Enteral Nutrition/trends
Japan
Adult
*Respiration, Artificial/trends
*Clinical Decision-Making
Age Factors

@article {pmid39954710,
year = {2025},
author = {Nadeem, ZA and Ahmed, S},
title = {Amyotrophic lateral sclerosis and lovastatin: a promising treatment perspective.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {5-6},
pages = {595-596},
doi = {10.1080/21678421.2025.2463943},
pmid = {39954710},
issn = {2167-9223},
}

@article {pmid39954940,
year = {2025},
author = {Satao, KS and Doshi, GM},
title = {Intercellular communication via exosomes: A new paradigm in the pathophysiology of neurodegenerative disorders.},
journal = {Life sciences},
volume = {365},
number = {},
pages = {123468},
doi = {10.1016/j.lfs.2025.123468},
pmid = {39954940},
issn = {1879-0631},
mesh = {Humans ; *Exosomes/metabolism/physiology ; *Neurodegenerative Diseases/physiopathology/metabolism/pathology ; *Cell Communication/physiology ; Animals ; },
abstract = {Neurodegenerative disorders are one of the leading causes of death and disability and pose a great economic burden on healthcare systems. Generally, these neurodegenerative disorders have a progressive deterioration in neural function and structure, and deposition of misfolded proteins commonly occurs, such as amyloid-β in AD and α-synuclein in PD. However, there exists a special class of exosomes, which acts like a transmitter and enhances communication between cells. The present review discusses the significant role of exosomes in neurodegenerative diseases, with a focus on Amyotrophic lateral Sclerosis (ALS), AD, PD, and Huntington's disease (HD). In this review, the biogenesis of exosomes is discussed from multivesicular bodies and onwards to their release into the extracellular environment. The present review focuses on recent data concerning the possible use of modified exosomes as ND therapy. Indeed, future work is needed to explain the processes driving exosome biogenesis and cargo selection, while opening new routes by the use of exosome-based therapeutics in neurodegenerative disease diagnosis and treatment.},
}

Humans
*Exosomes/metabolism/physiology
*Neurodegenerative Diseases/physiopathology/metabolism/pathology
*Cell Communication/physiology
Animals

@article {pmid39957320,
year = {2025},
author = {Lubbers-Wolterink, R and van Os-Medendorp, H and Jansen Klomp, W and Kamphorst, K},
title = {Exploring patient, informal caregiver, and nurse experiences with home-based hospital-level care for decompensated heart failure: a mixed-methods study.},
journal = {European journal of cardiovascular nursing},
volume = {24},
number = {4},
pages = {569-577},
doi = {10.1093/eurjcn/zvaf025},
pmid = {39957320},
issn = {1873-1953},
mesh = {Humans ; *Heart Failure/nursing/therapy ; *Caregivers/psychology ; Female ; Male ; Middle Aged ; Aged ; *Home Care Services, Hospital-Based ; *Patient Satisfaction ; Adult ; Surveys and Questionnaires ; Aged, 80 and over ; *Attitude of Health Personnel ; Qualitative Research ; Quality of Health Care ; },
abstract = {AIMS: Hospitals are encouraged to provide care closer to patients' homes. This study investigates how patients, informal caregivers, and nurses experience home-based hospital-level care for decompensated heart failure.

METHODS AND RESULTS: This mixed-methods study employed semi-structured interviews with 11 patients and 4 informal caregivers, a questionnaire administrated to 16 nurses from the intensive care, cardiac care, and general cardiology ward, and interviews with 4 nurses, supplemented by two group discussions.A convenience sample was utilized, member checks were performed, and two researchers analysed the patient interviews using thematic analysis based on the normalization process theory. Five overarching themes emerged: (i) Appreciation of personal environment, routines, and autonomy. (ii) Quality of care. (iii) Commitment to the treatment. (iv) Influence of personal characteristics. (v) Changing role of informal caregivers.Regarding nurse satisfaction, findings were mapped according to Proctor et al.'s implementation outcomes: acceptability: hospital-at-home care increases job satisfaction, through increased autonomy, personalized care, and patient satisfaction; appropriateness: hospital-at-home was perceived positively, although safety and adherence needed attention; adoption: hospital-at-home was not particularly challenging but offered a refreshing change; feasibility: on-call duty impacted personal commitments for some nurses; fidelity: information folders with clear protocols were deemed helpful.

CONCLUSION: Patients, caregivers, and nurses generally favour home-based heart failure treatment over hospital-based treatment. Key conditions include comprehensive education on home treatment, adherence support like dietary restriction maintenance, prioritizing patient autonomy, recognizing caregiver burden, and exploring cost-effective strategies such as collaboration with home care organizations.},
}

Humans
*Heart Failure/nursing/therapy
*Caregivers/psychology
Female
Male
Middle Aged
Aged
*Home Care Services, Hospital-Based
*Patient Satisfaction
Adult
Surveys and Questionnaires
Aged, 80 and over
*Attitude of Health Personnel
Qualitative Research
Quality of Health Care

@article {pmid39958442,
year = {2025},
author = {Ozbey, D and Saribas, S and Kocazeybek, B},
title = {Gut microbiota in Crohn's disease pathogenesis.},
journal = {World journal of gastroenterology},
volume = {31},
number = {6},
pages = {101266},
pmid = {39958442},
issn = {2219-2840},
mesh = {Humans ; Colon/microbiology/pathology/immunology ; *Crohn Disease/therapy/microbiology/immunology/pathology ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Ileum/microbiology/pathology/immunology ; Intestinal Mucosa/microbiology/pathology/immunology ; Treatment Outcome ; },
abstract = {Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.},
}

Humans
Colon/microbiology/pathology/immunology
*Crohn Disease/therapy/microbiology/immunology/pathology
Dysbiosis/therapy
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome/immunology
Ileum/microbiology/pathology/immunology
Intestinal Mucosa/microbiology/pathology/immunology
Treatment Outcome

@article {pmid39958549,
year = {2025},
author = {Zhang, Y},
title = {Enhancing rectal cancer liver metastasis prediction: Magnetic resonance imaging-based radiomics, bias mitigation, and regulatory considerations.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {2},
pages = {102151},
pmid = {39958549},
issn = {1948-5204},
abstract = {In this article, we comment on the article by Long et al published in the recent issue of the World Journal of Gastrointestinal Oncology. Rectal cancer patients are at risk for developing metachronous liver metastasis (MLM), yet early prediction remains challenging due to variations in tumor heterogeneity and the limitations of traditional diagnostic methods. Therefore, there is an urgent need for non-invasive techniques to improve patient outcomes. Long et al's study introduces an innovative magnetic resonance imaging (MRI)-based radiomics model that integrates high-throughput imaging data with clinical variables to predict MLM. The study employed a 7:3 split to generate training and validation datasets. The MLM prediction model was constructed using the training set and subsequently validated on the validation set using area under the curve (AUC) and dollar-cost averaging metrics to assess performance, robustness, and generalizability. By employing advanced algorithms, the model provides a non-invasive solution to assess tumor heterogeneity for better metastasis prediction, enabling early intervention and personalized treatment planning. However, variations in MRI parameters, such as differences in scanning resolutions and protocols across facilities, patient heterogeneity (e.g., age, comorbidities), and external factors like carcinoembryonic antigen levels introduce biases. Additionally, confounding factors such as diagnostic staging methods and patient comorbidities require further validation and adjustment to ensure accuracy and generalizability. With evolving Food and Drug Administration regulations on machine learning models in healthcare, compliance and careful consideration of these regulatory requirements are essential to ensuring safe and effective implementation of this approach in clinical practice. In the future, clinicians may be able to utilize data-driven, patient-centric artificial intelligence (AI)-enhanced imaging tools integrated with clinical data, which would help improve early detection of MLM and optimize personalized treatment strategies. Combining radiomics, genomics, histological data, and demographic information can significantly enhance the accuracy and precision of predictive models.},
}

@article {pmid39960672,
year = {2025},
author = {Paganoni, S and Fournier, CN and Macklin, EA and Chibnik, LB and Quintana, M and Saville, BR and Detry, MA and Vestrucci, M and Marion, J and McGlothlin, A and Ajroud-Driss, S and Chase, M and Pothier, L and Harkey, BA and Yu, H and Sherman, AV and Shefner, JM and Hall, M and Kittle, G and Berry, JD and Babu, S and Andrews, J and Dagostino, D and Tustison, E and Giacomelli, E and Scirocco, E and Alameda, G and Locatelli, E and Ho, D and Quick, A and Katz, J and Heitzman, D and Appel, SH and Shroff, S and Felice, K and Maragakis, NJ and Simmons, Z and Miller, TM and Olney, N and Weiss, MD and Goutman, SA and Fernandes, JA and Jawdat, O and Owegi, MA and Foster, LA and Vu, T and Ilieva, H and Newman, DS and Arcila-Londono, X and Jackson, CE and Ladha, S and Heiman-Patterson, T and Caress, JB and Swenson, A and Peltier, A and Lewis, R and Fee, D and Elliott, M and Bedlack, R and Kasarskis, EJ and Elman, L and Rosenfeld, J and Walk, D and McIlduff, C and Twydell, P and Young, E and Johnson, K and Rezania, K and Goyal, NA and Cohen, JA and Benatar, M and Jones, V and Glass, J and Shah, J and Beydoun, SR and Wymer, JP and Zilliox, L and Nayar, S and Pattee, GL and Martinez-Thompson, J and Harvey, B and Patel, S and Mahoney, P and Duda, PW and Cudkowicz, ME and , },
title = {Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {8},
number = {2},
pages = {e2459058},
pmid = {39960672},
issn = {2574-3805},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Middle Aged ; Double-Blind Method ; Aged ; Treatment Outcome ; },
abstract = {IMPORTANCE: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression.

OBJECTIVE: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS.

Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens.

INTERVENTIONS: Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing.

MAIN OUTCOMES AND MEASURES: The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; <1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164).

RESULTS: Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04297683.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
Male
Female
Middle Aged
Double-Blind Method
Aged
Treatment Outcome

@article {pmid39961673,
year = {2025},
author = {Aryapadi, V and Trivedi, J},
title = {Atypical presentation of amyotrophic lateral sclerosis with SOD1-H47R mutation.},
journal = {BMJ case reports},
volume = {18},
number = {2},
pages = {},
doi = {10.1136/bcr-2024-263293},
pmid = {39961673},
issn = {1757-790X},
mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/physiopathology ; Mutation ; *Superoxide Dismutase/genetics ; *Superoxide Dismutase-1/genetics ; },
abstract = {Traditionally, amyotrophic lateral sclerosis (ALS) is recognised as a fatal neurodegenerative disease that typically emerges in the later decades of life, with a life expectancy of 2-5 years after symptom onset. We now understand that ALS exhibits a wide phenotypic clinical spectrum, significantly influenced by genetic factors. Here, we describe a patient with familial ALS carrying a heterozygous pathogenic H47R mutation of the superoxide dismutase 1 (SOD1) gene. His clinical presentation is atypical, with a slow progressive course, lower extremity weakness, and sparing of bulbar and respiratory function, consistent with the flail leg variant of ALS. The objective of this report is to increase awareness of atypical presentations of ALS and the diagnostic challenges they pose to clinicians. In addition to a description of the clinical case, we briefly discuss the new role of gene therapy in the treatment of familial ALS with SOD1 mutations.},
}

Humans
Male
*Amyotrophic Lateral Sclerosis/genetics/diagnosis/physiopathology
Mutation
*Superoxide Dismutase/genetics
*Superoxide Dismutase-1/genetics

@article {pmid39963928,
year = {2025},
author = {Lomas, C and Dubey, RC and Perez-Alvarez, G and Lopez Hernandez, Y and Atmar, A and Arias, AY and Vashist, A and Aggarwal, S and Manickam, P and Lakshmana, MK and Vashist, A},
title = {Recent advances in nanotherapeutics for HIV-associated neurocognitive disorders and substance use disorders.},
journal = {Nanomedicine (London, England)},
volume = {20},
number = {6},
pages = {603-619},
pmid = {39963928},
issn = {1748-6963},
support = {R01 DA049657/DA/NIDA NIH HHS/United States ; R03 AG087475/AG/NIA NIH HHS/United States ; U01 ES033265/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Substance-Related Disorders/drug therapy/therapy ; Blood-Brain Barrier/metabolism ; *Nanomedicine/methods ; *HIV Infections/complications/drug therapy ; *Nanoparticles/chemistry/therapeutic use ; Animals ; *Neurocognitive Disorders/drug therapy ; *AIDS Dementia Complex/drug therapy ; },
abstract = {Substance use disorders (SUD) and HIV-associated neurocognitive disorders (HAND) work synergistically as a significant cause of cognitive decline in adults and adolescents globally. Current therapies continue to be limited due to difficulties crossing the blood-brain barrier (BBB) leading to limited precision and effectiveness, neurotoxicity, and lack of co-treatment options for both HAND and SUD. Nanoparticle-based therapeutics have several advantages over conventional therapies including more precise targeting, the ability to cross the BBB, and high biocompatibility which decreases toxicity and optimizes sustainability. These advantages extend to other neurological disorders such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). This review summarizes recent advances in nanotechnology for application to HAND, SUD, and co-treatment, as well as other neurological disorders. This review also highlights the potential challenges these therapies face in clinical translation and long-term safety.},
}

Humans
*Substance-Related Disorders/drug therapy/therapy
Blood-Brain Barrier/metabolism
*Nanomedicine/methods
*HIV Infections/complications/drug therapy
*Nanoparticles/chemistry/therapeutic use
Animals
*Neurocognitive Disorders/drug therapy
*AIDS Dementia Complex/drug therapy

@article {pmid39966966,
year = {2025},
author = {Downs, J},
title = {Eating disorders, dentistry, and the need for shared learning: a lived experience commentary on Gidlund et al.},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {35},
pmid = {39966966},
issn = {2050-2974},
abstract = {This Commentary builds upon the findings of Gidlund et al.'s study on the oral health experiences of women in remission from eating disorders. By exploring the nuanced and deeply embodied dimensions of oral health in eating disorders, their findings also highlight the intersectional challenges faced by individuals when accessing dental care, including stigma, shame, and ambivalence about treatment. Drawing on lived experience examples and published research, this Commentary aims to add to existing evidence demonstrating the need for a more integrated, patient-centred approach to both dental and eating disorders treatment, advocating for harm-reduction strategies to prevent and minimise damage during active illness alongside more inclusive and nuanced conceptualisations of illness, treatment, and recovery. Recommendations are made to adopt non-stigmatising language, expand demographic diversity in research, and to co-produce research and treatment provision alongside people with lived experience. The bidirectional relationship between oral health and eating disorder symptoms requires the creation of greater collaboration between dentistry and ED treatment providers, where shared learning and co-produced training can improve care pathways and address systemic gaps in knowledge and treatment.},
}

@article {pmid39967643,
year = {2025},
author = {Abdel-Magid, AF},
title = {Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors as Potential Treatment for Several Inflammatory and Neurodegenerative Diseases.},
journal = {ACS medicinal chemistry letters},
volume = {16},
number = {2},
pages = {204-206},
pmid = {39967643},
issn = {1948-5875},
abstract = {The invention in this patent application relates to 2-amino-[1,2,4]triazolo[1,5-a]pyridin derivatives represented generally herein as formula 1. These compounds have activities as receptor-interacting protein kinase 1 (RIPK1) inhibitors and may potentially provide treatment and/or prophylaxis of inflammatory and neurodegenerative diseases associated with aberrant RIPK1 activity such as ulcerative colitis, Crohn's disease, psoriasis, NASH, heart failure, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease.},
}

@article {pmid39968231,
year = {2025},
author = {Nagadi, E and Muryani, A and Adang, RAF},
title = {Integrated Endodontic and Restorative Management of C-Shaped Canals with Severe Coronal Loss in Mandibular Second Molar: A Case Report.},
journal = {Clinical, cosmetic and investigational dentistry},
volume = {17},
number = {},
pages = {121-134},
pmid = {39968231},
issn = {1179-1357},
abstract = {This case report describes the endodontic treatment of a lower right second molar with a C-shaped root canal in a 49-year-old woman exhibiting severe loss of coronal structure. Clinical examination revealed a cavity with temporary filling on tooth 47, which tested negative to cold stimuli but was positive to percussion and bite tests. Cone beam computed tomography (CBCT) scan revealed a C-shaped canal morphology with associated periapical radiolucency, graded as CBCT-PAI score 4. The canal was classified as C3 subdivision III (Melton et al), C3 type II (Fan et al), and [2]47 M[2-2]D[2-1] (Ahmed et al's). A non-surgical endodontic procedure was performed using metallurgically gold heat-treated files, passive ultrasonic irrigation, and warm hydraulic condensation obturation. Post-endodontic restoration included a post and core build-up with the wallpapering technique and a zirconia overlay. This case highlights the importance of CBCT imaging for diagnosis and treatment planning, careful selection of endodontic instruments and technique, and the use of advanced restoration methods to improve the outcome of challenging C-shaped canal treatments with extensive cavity involvement.},
}

@article {pmid39976261,
year = {2025},
author = {Menendez-Gonzalez, M},
title = {Implementing a tridimensional diagnostic framework for personalized medicine in neurodegenerative diseases.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {2},
pages = {e14591},
pmid = {39976261},
issn = {1552-5279},
support = {PI21/00467//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/diagnosis/genetics ; Biomarkers ; Neuroimaging ; },
abstract = {Neurodegenerative diseases (NDDs) pose a significant challenge in modern medicine due to their clinical heterogeneity, multifactorial etiologies, and frequent co-pathologies. Traditional diagnostic systems, based on clinical symptoms and post mortem findings, are limited in capturing the complex interactions among genetic, molecular, and neuroanatomical factors. This manuscript introduces a novel tridimensional diagnostic framework that integrates these factors across three key axes: etiology (genetic and environmental influences), molecular markers (primary and secondary biomarkers), and neuroanatomoclinical correlations. Through case studies, we demonstrate the framework's ability to synthesize incomplete datasets, stratify patients, and guide precision medicine. By incorporating omics technologies, neuroimaging, and AI-driven probabilistic modeling, the framework enhances diagnostic accuracy and clinical relevance. This approach may contribute to overcoming the limitations of traditional nosologies, offering a scalable and adaptable tool for both clinical practice and research and advancing the field of precision medicine in NDD management. HIGHLIGHTS: Tridimensional diagnostic system: We propose a new framework that incorporates three axes - etiology, molecular markers, and neuroanatomical-clinical correlations - to enhance diagnostic accuracy for NDDs. Personalized medicine: The tridimensional system enables the integration of genetic, molecular, and clinical data, allowing for highly personalized treatment strategies tailored to individual patients. Proteinopathies as key biomarkers: This diagnostic system emphasizes the use of primary proteinopathies (amyloid, tau, synuclein) and secondary biomarkers (eg, NfL, GFAP) to monitor disease progression and treatment efficacy. Addressing clinical heterogeneity: The framework accommodates the complexity and heterogeneity of NDDs, offering an adaptable diagnostic approach for classical conditions like Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and ALS. Case studies and real-world application: Practical case studies illustrate how this system can be implemented in clinical practice, enabling the combination of DMTs with symptomatic treatments.},
}

Humans
*Precision Medicine/methods
*Neurodegenerative Diseases/diagnosis/genetics
Biomarkers
Neuroimaging

@article {pmid39980064,
year = {2025},
author = {Downs, J},
title = {Furthering the benefits of DBT for eating disorders: a lived experience correspondence on McColl et al.},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {37},
pmid = {39980064},
issn = {2050-2974},
abstract = {This Correspondence article provides a lived experience perspective on McColl et al.'s study, which examines the use of Dialectical Behaviour Therapy for individuals with eating disorders. Drawing on experiences of DBT treatment for longstanding and severe anorexia, the author critically engages with the study's findings, highlighting both the strengths and limitations of the treatment approach McColl et al. describe. While DBT has shown promise in addressing the emotional dysregulation and distress tolerance that underlie many eating disorder behaviours, the author emphasises the need for further adaptation to cater to the complexities of co-occurring physical, psychological, and neurodivergent conditions. The benefits of DBT for eating disorders are explored through personal reflections which emphasise the value and importance of skill-development, therapeutic validation, and motivation to build a "life worth living". Additional, co-produced research is required to further develop the evidence for DBT-based approaches, with particular attention needed in addressing language, stigma, cultural biases, and exclusionary research and clinical practices. Writing from a UK context, the author ends by advocating for the reinstatement of DBT within national guidelines for eating disorder treatment, highlighting its transdiagnostic relevance and potential to provide comprehensive, holistic support for those with more complex presentations.},
}

@article {pmid39981400,
year = {2025},
author = {Yang, EJ and Lee, SH},
title = {Herbal Medicine Extracts Improve Motor Function by Anti-Inflammatory Activity in hSOD1[G93A] Animal Model.},
journal = {Mediators of inflammation},
volume = {2025},
number = {},
pages = {1999953},
pmid = {39981400},
issn = {1466-1861},
mesh = {Animals ; Mice ; Mice, Transgenic ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Disease Models, Animal ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Plant Extracts/therapeutic use/pharmacology ; Muscle, Skeletal/drug effects/metabolism ; Motor Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; *Herbal Medicine ; Male ; Superoxide Dismutase-1/metabolism/genetics ; Spinal Cord/drug effects/metabolism ; Inflammation/drug therapy ; Paeonia/chemistry ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multicomplex neurodegenerative disorder characterized by motor neuron death, muscle atrophy, and respiratory failure. Owing to its multicomplex mechanisms and multifactorial nature in the skeletal muscle and spinal cord (SC), no effective therapy has been developed. However, herbal medicines, known for their multitarget properties, have demonstrated promising efficacy with limited side effects in treating various diseases. Specifically, Paeonia lactiflora Pallas has been demonstrated to exhibit analgesic, antidepressant, anti-inflammatory, and neuroprotective effects. However, the pharmacological mechanisms underlying the beneficial effects of P. lactiflora in hSOD1[G93A] animal models remain unexplored. Therefore, this study was conducted to investigate the multitarget effects of P. lactiflora in hSOD1[G93A] transgenic mice, an ALS model. Footprint tests, western blot assays, and immunohistochemical analysis were used to assess the effect of P. lactiflora on the tibia anterior (TA), gastrocnemius (GC), and SC. The results revealed that P. lactiflora augmented motor function and decreased motor neuron loss in hSOD1[G93A] mice. Furthermore, P. lactiflora significantly lowered the expression of proteins associated with inflammation and oxidative stress in the skeletal muscle (TA and GC) and SC. P. lactiflora also regulated autophagy function by reducing the levels of key markers, such as P62/sequestosome 1 (SQSTM1), microtubule-associated proteins 1A/1B light chain 3B, and SMAD family member 2, in the muscle and SC. Overall, P. lactiflora treatment improved motor function, prevented motor neuron death, and exhibited anti-inflammatory and antioxidative effects in the skeletal muscle and SC of ALS mouse models. These results suggest that P. lactiflora could serve as a promising multitarget therapeutic agent for systemic and multipathological diseases.},
}

Animals
Mice
Mice, Transgenic
*Anti-Inflammatory Agents/therapeutic use/pharmacology
Disease Models, Animal
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
*Plant Extracts/therapeutic use/pharmacology
Muscle, Skeletal/drug effects/metabolism
Motor Neurons/drug effects/metabolism
Oxidative Stress/drug effects
*Herbal Medicine
Male
Superoxide Dismutase-1/metabolism/genetics
Spinal Cord/drug effects/metabolism
Inflammation/drug therapy
Paeonia/chemistry

@article {pmid39982687,
year = {2025},
author = {Loher, P and Londin, E and Ilieva, H and Pasinelli, P and Rigoutsos, I},
title = {Re-Analyses of Samples From Amyotrophic Lateral Sclerosis Patients and Controls Identify Many Novel Small RNAs With Diagnostic And Prognostic Potential.},
journal = {Molecular neurobiology},
volume = {62},
number = {7},
pages = {8135-8149},
pmid = {39982687},
issn = {1559-1182},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood ; Prognosis ; Male ; Female ; Case-Control Studies ; Middle Aged ; *MicroRNAs/genetics/blood ; Biomarkers/blood ; RNA, Ribosomal/genetics/blood ; Aged ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease for which accurate diagnostic and prognostic biomarkers are needed. Toward this goal, we reanalyzed two published collections of datasets generated from the plasma and serum of ALS patients and controls. We profiled these datasets for isoforms of microRNAs (miRNAs) known as isomiRs, transfer RNA-derived fragments (tRFs), and ribosomal RNA-derived fragments (rRFs), placing all remaining reads into a group labeled "not-itrs." We found that plasma and serum are rich in isomiRs (canonical, non-canonical, and non-templated), tRFs, rRFs, and members of an emerging class of small RNAs known as Y RNA-derived fragments (yRFs). In both analyzed collections, we found many isomiRs, tRFs, rRFs, and yRFs that are differentially abundant between patients and controls. We also performed a survival analysis that considered Riluzole treatment status, demographics (age at onset, age at enrollment, sex), and disease characteristics (ALSFRS, rD50, onset type) and found many of the differentially abundant small RNAs to be associated with survival time, with some of these associations being independent of Riluzole treatment. Unexpectedly, many not-itrs that did not map to the human genome mapped exactly to sequences from the SILVA database of ribosomal DNAs (rDNAs). Not-itrs from the plasma datasets mapped primarily to rDNAs from the order of Burkholderiales, and several of them were associated with patient survival. Not-itrs from the serum datasets also showed support for rDNA from Burkholderiales but a stronger support for rDNAs from the fungi group of the Nucletmycea taxon. The findings suggest that many previously unexplored small non-coding RNAs, including human isomiRs, tRFs, rRFs, and yRFs, could potentially serve as novel diagnostic and prognostic biomarkers for ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood
Prognosis
Male
Female
Case-Control Studies
Middle Aged
*MicroRNAs/genetics/blood
Biomarkers/blood
RNA, Ribosomal/genetics/blood
Aged

@article {pmid39985812,
year = {2025},
author = {Filippi, M and Ghirelli, A and Spinelli, EG and Agosta, F},
title = {A comprehensive update on neuroimaging endpoints in amyotrophic lateral sclerosis.},
journal = {Expert review of neurotherapeutics},
volume = {25},
number = {4},
pages = {397-413},
doi = {10.1080/14737175.2025.2470324},
pmid = {39985812},
issn = {1744-8360},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/therapy ; *Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; Positron-Emission Tomography/methods ; Disease Progression ; Biomarkers ; },
abstract = {INTRODUCTION: There are currently few treatments approved for amyotrophic lateral sclerosis (ALS). Additionally, there remains a significant unmet need for reliable, standardized biomarkers to assess endpoints in clinical trials. Magnetic resonance imaging (MRI)- and positron emission tomography (PET)-derived metrics could help in patient selection and stratification, shortening trial duration and reducing costs.

AREAS COVERED: This review focuses on the potential use of neuroimaging endpoints in the context of ALS therapeutic trials, providing insights on structural and functional neuroimaging, plexus and muscle alterations, glial involvement and neuroinflammation, envisioning how these surrogates of disease progression could be implemented in clinical trials. A PubMed search covering the past 15 years was performed.

EXPERT OPINION: Neuroimaging is essential in understanding ALS pathophysiology, aiding in disease progression tracking and evaluating therapeutic interventions. High costs, limited accessibility, lack of standardization, and patient tolerability limit their use in routine ALS care. Addressing these obstacles is essential for fully harnessing neuroimaging potential in improving diagnostics and treatment in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/therapy
*Neuroimaging/methods
Magnetic Resonance Imaging/methods
Positron-Emission Tomography/methods
Disease Progression
Biomarkers

@article {pmid39987111,
year = {2025},
author = {Zeng, L and Yang, F and Xu, D and Zhou, J and Qiao, G and Wu, M and Li, C and Yu, Y and Qiu, Y and Liu, J},
title = {Actual needs of patients with amyotrophic lateral sclerosis: a qualitative study from Wuhan, China.},
journal = {BMC palliative care},
volume = {24},
number = {1},
pages = {50},
pmid = {39987111},
issn = {1472-684X},
support = {2023AFD160//Hubei Provincial Natural Science Foundation and Traditional Chinese Medicine Innovation and Development Joint/ ; 2024AFD279//Department of Science and Technology, Hubei Province, China/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; China ; Qualitative Research ; Male ; Female ; Middle Aged ; Aged ; Adult ; Quality of Life/psychology ; *Health Services Needs and Demand ; *Needs Assessment ; Medicine, Chinese Traditional/methods ; Interviews as Topic/methods ; },
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disorder that significantly impacts individuals and families. Previous research on ALS has predominantly focused on its pathophysiology, genetic factors, and potential therapeutic interventions. While these aspects are essential for understanding and treating the disease, there has been a growing recognition of the importance of studying patients' actual needs. Understanding these needs is vital for developing patient-centered care models that can enhance the well-being of ALS patients. However, existing studies on patients' needs are often limited in scope. Many are conducted in Western countries, and the results may not be directly applicable to patients in other cultural and socioeconomic contexts. China, with its large population and diverse cultural, economic, and healthcare landscapes, presents a unique setting for studying ALS patients' needs. At the same time, traditional Chinese medicine (TCM) practices are deeply ingrained in their healthcare system and may affect the way people with ALS seek treatment and manage their condition. Therefore, these differences may lead to differences in the actual needs of ALS patients in China. In conclusion, this qualitative study on the actual needs of ALS patients in China aims to bridge the gap in the existing research. By exploring these needs, it can provide valuable insights for healthcare providers, policymakers, and researchers, ultimately contributing to the improvement of care and quality of life for ALS patients in China.

METHOD: We carried out a qualitative study using an empirical phenomenological approach. Individual in-depth interviews were performed among 22 people with ALS from the motor neuron disease rehabilitation center of a tertiary Chinese medicine hospital in China, and the interview content was analyzed qualitatively. Interview recordings were converted to text content by NVivo 11.0 software and analyzed using Colaizzi's phenomenological method.

RESULT: Three main themes were identified in this study: (1) Demand for healthcare services, (2) Emotional requirements, (3) Functional requirements. In addition, 8 sub-themes were extracted as the actual needs of ALS patients.

CONCLUSION: This study is based on the real experience of ALS patients after diagnosis, and a deep understanding of these experiences can explore the actual needs of patients from many aspects and give reasonable advice and help. Given the particularity of the disease and the uncertainty of treatment, patients will have practical needs for relevant medical support, emotional requirements, physical functions, and other aspects during the period of illness, and the corresponding support is an effective measure to reduce the burden on patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/therapy/complications
China
Qualitative Research
Male
Female
Middle Aged
Aged
Adult
Quality of Life/psychology
*Health Services Needs and Demand
*Needs Assessment
Medicine, Chinese Traditional/methods
Interviews as Topic/methods

@article {pmid39987285,
year = {2025},
author = {Fang, M and Zhou, Y and He, K and Lu, Y and Tao, F and Huang, H},
title = {Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.},
journal = {Molecular neurobiology},
volume = {62},
number = {7},
pages = {8204-8221},
pmid = {39987285},
issn = {1559-1182},
support = {82204651//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Microglia/metabolism/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology/therapy ; *Glucose/metabolism ; Animals ; *Molecular Targeted Therapy ; Glycolysis ; Metabolic Reprogramming ; },
abstract = {As intrinsic immune cells in the central nervous system, microglia play a crucial role in maintaining brain homeostasis. Microglia can transition from homeostasis to various responsive states in reaction to different external stimuli, undergoing corresponding alterations in glucose metabolism. In neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), microglial glucose metabolic reprogramming is widespread. This reprogramming leads to changes in microglial function, exacerbating neuroinflammation and the accumulation of pathological products, thereby driving the progression of neurodegeneration. This review summarizes the specific alterations in glucose metabolism within microglia in AD, PD, ALS, and MS, as well as the corresponding treatments aimed at reprogramming glucose metabolism. Compounds that inhibit key glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), or activate regulators of energy metabolism such as AMP-activated protein kinase (AMPK), have shown significant potential in the treatment of various neurodegenerative diseases. However, current research faces numerous challenges, including side effects and blood-brain barrier (BBB) penetration of compounds. Screening relevant drugs from natural products, especially flavonoids, is a reliable approach. On the one hand, longtime herbal medical practices provide a certain degree of assurance regarding clinical safety, and their chemical properties contribute to effective BBB permeability. On the other hand, the concurrent anti-tumor and anti-neuroinflammatory activities of flavonoids suggest that regulation of glucose metabolism reprogramming might be a potential common mechanism of action. Notably, considering the dynamic nature of microglial metabolism, there is an urgent need to develop technologies for real-time monitoring of glucose metabolism processes, which would significantly advance research in this field.},
}

Humans
*Microglia/metabolism/drug effects
*Neurodegenerative Diseases/metabolism/drug therapy/pathology/therapy
*Glucose/metabolism
Animals
*Molecular Targeted Therapy
Glycolysis
Metabolic Reprogramming

@article {pmid39992655,
year = {2025},
author = {Liu, X and Shang, H and Wei, Q and Yao, X and Lian, L and Dang, J and Jia, R and Wu, Z and Li, H and Niu, Q and Cheng, X and Zou, Z and Chen, S and Zhang, M and Liu, Y and Liu, Y and Liu, Q and Huang, X and Wang, H and Feng, H and Wang, S and Fan, D and , },
title = {Tetramethylpyrazine Nitrone in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {8},
number = {2},
pages = {e2461055},
pmid = {39992655},
issn = {2574-3805},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Pyrazines/therapeutic use/administration & dosage ; Male ; Female ; Middle Aged ; Aged ; Double-Blind Method ; China ; Treatment Outcome ; },
abstract = {IMPORTANCE: Tetramethylpyrazine nitrone has exhibited promising results in improving motor dysfunction in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

OBJECTIVE: To evaluate the safety and efficacy of orally administered tetramethylpyrazine nitrone in patients with ALS.

This phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial was conducted from December 24, 2020, through July 14, 2023, in 11 centers in China, with a 180-day follow-up. Patients aged 45 to 70 years, with ALS onset within 2 years, ALS Functional Rating Scale-Revised (ALSFRS-R) scores of at least 2 points on each item, and forced vital capacity (FVC) of at least 80% were included. Patients experienced a 1- to 4-point decrease in ALSFRS-R score during a 3-month screening period.

INTERVENTIONS: Patients were randomly assigned 1:1:1 to receive low-dose tetramethylpyrazine nitrone (600 mg twice daily), high-dose tetramethylpyrazine nitrone (1200 mg twice daily), or placebo (twice daily) for 180 days.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in ALSFRS-R score (range of 0-48, with lower scores indicating worse function) from baseline to 180 days. The secondary outcomes were changes in FVC, grip strength, ALS Assessment Questionnaire-40 (ALSAQ-40) score, and end point events. Safety outcomes included adverse events.

RESULTS: A total of 155 patients (mean [SD] age, 55.0 [6.5] years; 115 men [74.2%]) were randomized (51 [32.9%] to the low-dose tetramethylpyrazine nitrone group, 52 [33.6%] to the high-dose tetramethylpyrazine nitrone group, and 52 [33.6%] to the placebo group). No significant differences were observed in ALSFRS-R score changes between low-dose tetramethylpyrazine nitrone (least squares [LS] mean difference, -0.89 points; 95% CI -3.25 to 1.48 points) and high-dose tetramethylpyrazine nitrone (LS mean difference, -0.20 points; 95% CI -2.48 to 2.07 points) compared with placebo. High-dose tetramethylpyrazine nitrone showed a significantly slower decline in grip strength at day 180 (LS mean difference, 2.46 kg; 95% CI, 0.15-4.76 kg). In a subgroup of patients younger than 65 years with slower disease progression, tetramethylpyrazine nitrone significantly attenuated the decline in grip strength (LS mean difference, 3.63 kg; 95% CI, 0.84-6.41 kg), bulbar scores (LS mean difference, 0.66 points; 95% CI, 0.03-1.29 points), and respiratory scores (LS mean difference, 0.54 points; 95% CI, 0.03-1.06 points). Adverse events were mostly mild or moderate, with no severe treatment-related adverse events or deaths.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial demonstrates that tetramethylpyrazine nitrone is safe and well-tolerated in patients with ALS. There was no difference in the primary end point across the low-dose, high-dose, and placebo groups, with significant benefits in a subgroup of younger patients with slower disease progression.

TRIAL REGISTRATION: ChiCTR Identifier: ChiCTR2000039689.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Pyrazines/therapeutic use/administration & dosage
Male
Female
Middle Aged
Aged
Double-Blind Method
China
Treatment Outcome

@article {pmid39995125,
year = {2025},
author = {Kalinin, AP and Zubkova, ES and Menshikov, MY and Parfyonova, YV},
title = {ISR Modulators in Neurological Diseases.},
journal = {Current neuropharmacology},
volume = {23},
number = {10},
pages = {1184-1214},
pmid = {39995125},
issn = {1875-6190},
support = {23-15-00539//Russian Science Foundation, RSF/ ; },
mesh = {Humans ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; *Signal Transduction/drug effects/physiology ; *Stress, Physiological/physiology/drug effects ; },
abstract = {The dysfunction of different cells lies in the pathogenesis of neurological diseases and is usually associated with cellular stress. Various stressors trigger the integrated stress response (ISR) signaling, whose highly conserved mechanism is primarily aimed at protecting a stress-exposed cell to cope as safely as possible with such stressful conditions. On the contrary, if a cell is unable to cope with excessive stress, the ISR can induce apoptosis. The ISR mechanism, whose main stage is the inhibition of translation machinery in favor of the synthesis of specific proteins, including the transcription factors ATF3, ATF4, CEBPA, and CEBPB, which function only as dimers and determine the uniqueness of the ISR response in each individual case, thus ensures different outcomes of the ISR. Inhibition of global protein synthesis is achieved through phosphorylation of eIF2α by PERK, HRI, PKR, or GCN2. To date, a number of compounds have been developed that modulate the ISR, including activators and inhibitors of the abovementioned ISR kinases as well as modulators of p-eIF2α dephosphorylation. They target different ISR stages, allowing a broad ISR modulation strategy. At the same time, there are no drugs that are both exceptionally safe and effective for the treatment of several neurological diseases, so there is an urgent need for new approaches to the treatment of these disorders. In this review, we represent ISR signaling as an important participant in the pathogenesis of neurological diseases. We also describe how various ISR modulators may become a part of future therapies for these diseases.},
}

Humans
*Nervous System Diseases/metabolism/drug therapy
Animals
*Signal Transduction/drug effects/physiology
*Stress, Physiological/physiology/drug effects

@article {pmid39996130,
year = {2025},
author = {Dilliott, AA and Costanzo, MC and Bandres-Ciga, S and Blauwendraat, C and Casey, B and Hoang, Q and Iwaki, H and Jang, D and Kim, JJ and Leonard, HL and Levine, KS and Makarious, M and Nguyen, TT and Rouleau, GA and Singleton, AB and Smadbeck, P and Solle, J and Vitale, D and Nalls, M and Flannick, J and Burtt, NP and Farhan, SMK},
title = {The Neurodegenerative Disease Knowledge Portal: Propelling Discovery Through the Sharing of Neurodegenerative Disease Genomic Resources.},
journal = {Neurology. Genetics},
volume = {11},
number = {2},
pages = {e200246},
pmid = {39996130},
issn = {2376-7839},
support = {U24 HG011453/HG/NHGRI NIH HHS/United States ; },
abstract = {Although large-scale genetic association studies have proven useful for the delineation of neurodegenerative disease processes, we still lack a full understanding of the pathologic mechanisms of these diseases, resulting in few appropriate treatment options and diagnostic challenges. To mitigate these gaps, the Neurodegenerative Disease Knowledge Portal (NDKP) was created as an open-science initiative with the aim to aggregate, enable analysis, and display all available genomic datasets of neurodegenerative disease, while protecting the integrity and confidentiality of the underlying datasets. The portal contains 218 genomic datasets, including genotyping and sequencing studies, of individuals across 10 different phenotypic groups, including neurologic conditions such as Alzheimer disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson disease. In addition to securely hosting large genomic datasets, the NDKP provides accessible workflows and tools to effectively use the datasets and assist in the facilitation of customized genomic analyses. Here, we summarize the genomic datasets currently included within the portal, the bioinformatics processing of the datasets, and the variety of phenotypes captured. We also present example use cases of the various user interfaces and integrated analytic tools to demonstrate their extensive utility in enabling the extraction of high-quality results at the source, for both genomics experts and those in other disciplines. Overall, the NDKP promotes open science and collaboration, maximizing the potential for discovery from the large-scale datasets researchers and consortia are expending immense resources to produce and resulting in reproducible conclusions to improve diagnostic and therapeutic care for patients with neurodegenerative disease.},
}

@article {pmid39998031,
year = {2025},
author = {Burke, KM and Shea, C and Arulanandam, V and Sullivan, S and Ellrodt, AS and MacAdam, C and Carney, K and Casagrande, G and Christiansen, E and Paganoni, S},
title = {Cervical Collar Satisfaction and Functional Impact in Amyotrophic Lateral Sclerosis: A Survey Study.},
journal = {American journal of physical medicine & rehabilitation},
volume = {104},
number = {9},
pages = {809-813},
doi = {10.1097/PHM.0000000000002716},
pmid = {39998031},
issn = {1537-7385},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/complications/physiopathology ; Female ; Male ; Middle Aged ; *Patient Satisfaction ; Aged ; Activities of Daily Living ; *Neck Pain/etiology/rehabilitation ; Cervical Vertebrae ; Quality of Life ; Adult ; Surveys and Questionnaires ; *Muscle Weakness/etiology/rehabilitation ; *Braces ; },
abstract = {OBJECTIVES: Many people with amyotrophic lateral sclerosis develop cervical muscle weakness, often managed with cervical collars. Finding supportive and comfortable collars can be challenging. This study aimed to evaluate satisfaction with various collars and their impact on activities of daily living.

DESIGN: This electronic survey study collected demographic information, clinical status, and participant experiences with commonly used cervical collars.

RESULTS: Thirty-four participants (33 with amyotrophic lateral sclerosis, 1 with primary lateral sclerosis) completed the survey, with 79% reporting neck weakness and 38% experiencing neck pain. Among those who tried cervical collars (65%), many had tried multiple options. The mean satisfaction across all collar types was 5.03 (SD = 2.92) out of 10.

CONCLUSIONS: These findings suggest current collars do not fully meet the needs of people living with amyotrophic lateral sclerosis, emphasizing the importance of improved treatment options. Future research should explore innovative technologies to improve cervical support, function, and quality of life.},
}

Humans
*Amyotrophic Lateral Sclerosis/rehabilitation/complications/physiopathology
Female
Male
Middle Aged
*Patient Satisfaction
Aged
Activities of Daily Living
*Neck Pain/etiology/rehabilitation
Cervical Vertebrae
Quality of Life
Adult
Surveys and Questionnaires
*Muscle Weakness/etiology/rehabilitation
*Braces

@article {pmid40000618,
year = {2025},
author = {Ru, Q and Li, Y and Zhang, X and Chen, L and Wu, Y and Min, J and Wang, F},
title = {Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.},
journal = {Bone research},
volume = {13},
number = {1},
pages = {27},
pmid = {40000618},
issn = {2095-4700},
support = {82071970//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82072506//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31970689//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32330047//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024AFB971//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; },
mesh = {Humans ; *Ferroptosis/physiology ; *Iron/metabolism ; *Homeostasis ; *Muscular Diseases/metabolism/pathology/therapy ; Animals ; Muscle, Skeletal/metabolism ; },
abstract = {The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.},
}

Humans
*Ferroptosis/physiology
*Iron/metabolism
*Homeostasis
*Muscular Diseases/metabolism/pathology/therapy
Animals
Muscle, Skeletal/metabolism

@article {pmid40001529,
year = {2025},
author = {Onu, CJ and Adu, M and Chakkour, M and Kumar, V and Greenberg, ML},
title = {Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders.},
journal = {Biomolecules},
volume = {15},
number = {2},
pages = {},
pmid = {40001529},
issn = {2218-273X},
support = {R01 GM125082/GM/NIGMS NIH HHS/United States ; R35 GM149271/GM/NIGMS NIH HHS/United States ; GM149271/GF/NIH HHS/United States ; GM125082/GF/NIH HHS/United States ; },
mesh = {Humans ; *Inositol Phosphates/metabolism ; *Neurodegenerative Diseases/metabolism/enzymology ; Animals ; Inositol/metabolism ; Signal Transduction ; },
abstract = {Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, metabolic flux, stress response, and other key biological processes. While emerging research has highlighted the significant roles of inositol phosphates in immunity, cancer, and metabolic diseases, there is a lack of comprehensive reviews on their roles in psychiatric and neurological disorders. This review aims to fill that gap by analyzing the existing literature on the importance of inositol phosphates in severe psychiatric and neurological conditions such as Parkinson's disease, Alzheimer's disease, bipolar disorder, amyotrophic lateral sclerosis, schizophrenia, and Huntington's disease, underscoring the potential to pave the way for new treatment regimens for these debilitating disorders targeting inositol pathways.},
}

Humans
*Inositol Phosphates/metabolism
*Neurodegenerative Diseases/metabolism/enzymology
Animals
Inositol/metabolism
Signal Transduction

@article {pmid40001624,
year = {2025},
author = {Ma, B and Ren, J and Qian, X},
title = {Study on the Polarization of Astrocytes in the Optic Nerve Head of Rats Under High Intraocular Pressure: In Vitro.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {40001624},
issn = {2306-5354},
support = {12472309 12072210//National Natural Science Foundation of China/ ; },
abstract = {Astrocytes, the most common glial cells in the optic nerve head (ONH), provide support and nutrition to retinal ganglion cells. This study aims to investigate the polarization types of astrocytes in the ONH of rats under high intraocular pressure (IOP) and explore signaling pathways potentially associated with different types of polarized astrocytes. The rat models with chronic high IOP were established. High IOP lasted for 2, 4, 6, and 8 weeks. Astrocytes were extracted from the ONH of rats using the tissue block cultivation method. Western blot was used to detect the expression of proteins associated with astrocyte polarization. Proteomics was employed to identify differential proteins associated with astrocyte polarization. Astrocytes polarized into A2 astrocytes after 2, 4, 6, and 8 weeks of high IOP, while polarization into A1 astrocytes began only after 8 weeks of high IOP. The differential proteins associated with A1 astrocyte polarization are primarily enriched in pathways of neurodegeneration with respect to multiple diseases, while the differential proteins associated with A2 astrocyte polarization are primarily enriched in pathways of spliceosome in amyotrophic lateral sclerosis. Our findings could provide a better understanding of the role of ONH astrocytes in the pathogenesis of glaucoma and offer new perspectives for glaucoma treatment.},
}

@article {pmid40002740,
year = {2025},
author = {Meng, K and Jia, H and Hou, X and Zhu, Z and Lu, Y and Feng, Y and Feng, J and Xia, Y and Tan, R and Cui, F and Yuan, J},
title = {Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
pmid = {40002740},
issn = {2227-9059},
support = {600791001//the Research Start-up Fund of Jining Medical University/ ; JYHL2021MS13//Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University/ ; 81700055//the National Natural Science Foundation of China/ ; Grant No. D2016021//Outstanding Talent Research Funding of Xuzhou Medical University/ ; BK20160229//Natural Science Foundation of Jiangsu Province/ ; tsqn201909147//Taishan Scholars Program of Shandong Province/ ; G2Y-kJS-SD-2023-097//Co-construction of Science and Technology Projects by the Science and Technology Department of the State Administration of Traditional Chinese Medicine/ ; },
abstract = {Neurodegenerative disease (ND) refers to the progressive loss and morphological abnormalities of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Examples of neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Recent studies have shown that mitochondria play a broad role in cell signaling, immune response, and metabolic regulation. For example, mitochondrial dysfunction is closely associated with the onset and progression of a variety of diseases, including ND, cardiovascular diseases, diabetes, and cancer. The dysfunction of energy metabolism, imbalance of mitochondrial dynamics, or abnormal mitophagy can lead to the imbalance of mitochondrial homeostasis, which can induce pathological reactions such as oxidative stress, apoptosis, and inflammation, damage the nervous system, and participate in the occurrence and development of degenerative nervous system diseases such as AD, PD, and ALS. In this paper, the latest research progress of this subject is detailed. The mechanisms of oxidative stress, mitochondrial homeostasis, and mitophagy-mediated ND are reviewed from the perspectives of β-amyloid (Aβ) accumulation, dopamine neuron damage, and superoxide dismutase 1 (SOD1) mutation. Based on the mechanism research, new ideas and methods for the treatment and prevention of ND are proposed.},
}

@article {pmid40007904,
year = {2025},
author = {Esteruelas, G and Ettcheto, M and Haro, I and Herrando-Grabulosa, M and Gaja-Capdevila, N and Gomara, MJ and Navarro, X and Espina, M and Souto, EB and Camins, A and García, ML and Sánchez-López, E},
title = {Novel Tissue-Specific Multifunctionalized Nanotechnological Platform Encapsulating Riluzole Against Motor Neuron Diseases.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {2273-2288},
pmid = {40007904},
issn = {1178-2013},
mesh = {*Riluzole/administration & dosage/pharmacokinetics/chemistry ; Animals ; *Nanoparticles/chemistry ; *Neuroprotective Agents/administration & dosage/pharmacokinetics/chemistry ; *Motor Neuron Disease/drug therapy ; Humans ; Motor Neurons/drug effects/metabolism ; Amyotrophic Lateral Sclerosis/drug therapy ; Drug Carriers/chemistry ; Mice ; Polyethylene Glycols/chemistry ; Drug Delivery Systems/methods ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Blood-Brain Barrier/metabolism ; },
abstract = {BACKGROUND: Motor neuron diseases are neurological disorders characterized by progressive degeneration of upper and/or lower motor neurons. Amyotrophic Lateral Sclerosis (ALS) is the most common form of motor neuron diseases, where patients suffer progressive paralysis, muscle atrophy and finally death. Despite ALS severity, no treatment is safe and fully effective. In this area, Riluzole was the first drug approved and it constitutes the gold-standard for this pathology. However, to obtain suitable therapeutic efficacy, Riluzole requires high doses that are associated with severe adverse effects in other tissues. To attain Riluzole therapeutic efficacy avoiding other organs side-effects, new therapeutic strategies to enhance the delivery of Riluzole specifically to motor neurons constitute an unmet medical need. In this area, we have developed a novel multifunctional nanostructurated carrier to selectively deliver Riluzole to motor neurons.

RESULTS: This work develops and characterizes at in vitro and in vivo levels a tissue-targeted formulation of peptide and PEG-labelled PLGA nanoparticles encapsulating Riluzole. For this purpose, pVEC, a cell penetrating peptide able to increase transport through the blood-brain barrier, was attached to the nanoparticles surface. The multifunctionalized nanoparticles show suitable characteristics for the release of Riluzole in the central nervous system and were detected in motor neurons within 1 h after administration while significantly reducing the concentration of Riluzole in non-therapeutic organs responsible of side effects.

CONCLUSION: A novel drug delivery system has been developed and characterized, demonstrating enhanced CNS biodistribution of riluzole, which shows promise as efficient therapeutic tool for motor neuron diseases, including amyotrophic lateral sclerosis.},
}

*Riluzole/administration & dosage/pharmacokinetics/chemistry
Animals
*Nanoparticles/chemistry
*Neuroprotective Agents/administration & dosage/pharmacokinetics/chemistry
*Motor Neuron Disease/drug therapy
Humans
Motor Neurons/drug effects/metabolism
Amyotrophic Lateral Sclerosis/drug therapy
Drug Carriers/chemistry
Mice
Polyethylene Glycols/chemistry
Drug Delivery Systems/methods
Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
Blood-Brain Barrier/metabolism

@article {pmid40008327,
year = {2025},
author = {van Eijk, RPA and Steyn, FJ and Janse van Mantgem, MR and Schmidt, A and Meyjes, M and Allen, S and Daygon, DV and Loeffler, JP and Al-Chalabi, A and van den Berg, LH and Henderson, RD and Ngo, ST},
title = {An open-label Phase 2a study to assess the safety and tolerability of trimetazidine in patients with amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {7},
number = {1},
pages = {fcaf063},
pmid = {40008327},
issn = {2632-1297},
abstract = {Metabolic imbalance is associated with amyotrophic lateral sclerosis progression. Impaired glucose oxidation and increased reliance on fatty acid oxidation contribute to reduced metabolic flexibility and faster disease progression in amyotrophic lateral sclerosis. We sought to evaluate the safety and tolerability, and explore the pharmacodynamic response of trimetazidine, a partial fatty acid oxidation inhibitor, on oxidative stress markers and energy expenditure in amyotrophic lateral sclerosis. The study was conducted between June 29, 2021 and May 24, 2023. People living with amyotrophic lateral sclerosis, recruited in Australia and the Netherlands, received open-label oral trimetazidine for 12 weeks after an initial 4-week lead-in period. The primary outcome measures were safety and tolerability, as well as the change from baseline in oxidative stress markers malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Secondary outcome measures were change from baseline in energy expenditure, amyotrophic lateral sclerosis functional rating scale-revised, and slow vital capacity (SVC). Linear mixed effects were used to estimate the mean difference in MDA and 8-OHdG between the on- and off-treatment periods. This trial is registered under ClinicalTrial.gov National Clinical Trial (NCT) number NCT04788745 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2020-005018-17. Twenty-one participants received trimetazidine; 19 (90%) completed the treatment period. Trimetazidine was well tolerated; there were 57 adverse events reported, of which 7 (11%) were deemed potentially drug-related, including hot flushes (2), nausea (2), paraesthesia (2) and fatigue (1). MDA was numerically lower during treatment [-0.29 uM; 95% confidence interval (CI) -0.90 to 0.33, P = 0.36]; 8-OHdG was significantly lower during treatment (-0.12 nM; 95% CI -0.23 to -0.01, P = 0.0245). The decrease in oxidative stress markers was accompanied by a reduction in resting energy expenditure (95 kcal, 95% CI 36.8-154, P = 0.0014). The absence of a placebo group prevented the interpretation of the clinical parameters. Oral trimetazidine was safe and well tolerated among patients with amyotrophic lateral sclerosis. This, combined with the significant reduction in markers of oxidative stress and resting energy expenditure, warrants a larger double-blind placebo-controlled efficacy study.},
}

@article {pmid40009238,
year = {2025},
author = {Ruffo, P and Traynor, BJ and Conforti, FL},
title = {Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects.},
journal = {Journal of neurology},
volume = {272},
number = {3},
pages = {233},
pmid = {40009238},
issn = {1432-1459},
support = {ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Genetic Therapy/methods/trends ; Animals ; },
abstract = {This review explores the intricate landscape of neurodegenerative disease research, focusing on Amyotrophic Lateral Sclerosis (ALS) and the intersection of genetics and RNA biology to investigate the causative pathogenetic basis of this fatal disease. ALS is a severe neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness and paralysis. Despite significant research advances, the exact cause of ALS remains largely unknown. Thanks to the application of next-generation sequencing (NGS) approaches, it was possible to highlight the fundamental role of rare variants with large effect sizes and involvement of portions of non-coding RNA, providing valuable information on risk prediction, diagnosis, and treatment of age-related diseases, such as ALS. Genetic research has provided valuable insights into the pathophysiology of ALS, leading to the development of targeted therapies such as antisense oligonucleotides (ASOs). Regulatory agencies in several countries are evaluating the commercialization of Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies. Furthermore, the emerging significance of microRNAs (miRNAs) and long RNAs are of great interest. MiRNAs have emerged as promising biomarkers for diagnosing ALS and monitoring disease progression. Understanding the role of lncRNAs in the pathogenesis of ALS opens new avenues for therapeutic intervention. However, challenges remain in delivering RNA-based therapeutics to the central nervous system. Advances in genetic screening and personalized medicine hold promise for improving the management of ALS. Ongoing clinical trials use genomic approaches for patient stratification and drug targeting. Further research into the role of non-coding RNAs in the pathogenesis of ALS and their potential as therapeutic targets is crucial to the development of effective treatments for this devastating disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/therapy
*Genetic Therapy/methods/trends
Animals

@article {pmid40009414,
year = {2025},
author = {Hamad, AA},
title = {Tofersen for Amyotrophic Lateral Sclerosis: Genetic Treatment With Precision Medicine: The Future of ALS Treatment.},
journal = {Journal of clinical neuromuscular disease},
volume = {26},
number = {3},
pages = {117-119},
doi = {10.1097/CND.0000000000000517},
pmid = {40009414},
issn = {1537-1611},
}

@article {pmid40010009,
year = {2025},
author = {Mikuriya, S and Takegawa-Araki, T and Tamura, M},
title = {Edaravone mitigates TDP-43 mislocalization in human amyotrophic lateral sclerosis neurons with potential implication of the SIRT1-XBP1 pathway.},
journal = {Free radical biology & medicine},
volume = {230},
number = {},
pages = {283-293},
doi = {10.1016/j.freeradbiomed.2025.01.012},
pmid = {40010009},
issn = {1873-4596},
mesh = {*Edaravone/pharmacology ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *X-Box Binding Protein 1/genetics/metabolism ; *Motor Neurons/drug effects/metabolism/pathology ; Induced Pluripotent Stem Cells/drug effects/metabolism ; *Sirtuin 1/metabolism/genetics ; Endoplasmic Reticulum Stress/drug effects ; Signal Transduction/drug effects ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss along with pathological mislocalization of TAR DNA-binding protein 43 (TDP-43), a protein implicated in RNA metabolism. Although edaravone, a free-radical scavenger, has been approved for ALS treatment, its precise mechanism of action is not fully understood, particularly in relation to TDP-43 pathology. Here, we investigated the effects of edaravone on induced pluripotent stem cell (iPSC)-derived motor neurons in a patient with ALS harboring a TDP-43 mutation. Our results demonstrated that edaravone significantly attenuated neurodegeneration, as evidenced by neurite preservation, neuronal cell death reduction, and correction of aberrant cytoplasmic localization of TDP-43. These neuroprotective effects were not observed with vitamin C, indicating a unique mechanism of action for edaravone, distinct from its antioxidative properties. RNA sequencing revealed that edaravone rapidly modulated gene expression, including protein quality control pathway, such as the ubiquitin-proteasome system. Further analysis identified X-box binding protein (XBP1), a key regulator of the endoplasmic reticulum stress response, as a critical factor in the therapeutic effects of edaravone. This study suggests that edaravone may offer a multifaceted therapeutic approach for ALS by targeting oxidative stress and TDP-43 mislocalization through distinct molecular pathways.},
}

*Edaravone/pharmacology
Humans
*Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology/metabolism
*DNA-Binding Proteins/genetics/metabolism
*X-Box Binding Protein 1/genetics/metabolism
*Motor Neurons/drug effects/metabolism/pathology
Induced Pluripotent Stem Cells/drug effects/metabolism
*Sirtuin 1/metabolism/genetics
Endoplasmic Reticulum Stress/drug effects
Signal Transduction/drug effects

@article {pmid40011434,
year = {2025},
author = {Gao, G and Shi, Y and Deng, HX and Krainc, D},
title = {Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson's disease models.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1982},
pmid = {40011434},
issn = {2041-1723},
support = {R21 NS114765/NS/NINDS NIH HHS/United States ; NS114765//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS099623/NS/NINDS NIH HHS/United States ; R35 NS122257/NS/NINDS NIH HHS/United States ; NS122257//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS099623//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {Animals ; *Mitochondria/metabolism/enzymology ; *Ketoglutarate Dehydrogenase Complex/metabolism/genetics ; Humans ; *Lipid Peroxidation/drug effects ; *Parkinson Disease/metabolism/genetics/pathology ; Male ; Mice ; Disease Models, Animal ; alpha-Synuclein/metabolism ; Dopaminergic Neurons/metabolism/drug effects ; *Transcription Factors/genetics/metabolism ; Mice, Knockout ; Thioctic Acid/pharmacology ; DNA-Binding Proteins/metabolism/genetics ; Brain/metabolism ; *Mitochondrial Proteins/metabolism/genetics ; Ketoglutaric Acids/metabolism ; Mice, Inbred C57BL ; },
abstract = {Dysregulation of mitochondrial function has been implicated in Parkinson's disease (PD), but the role of mitochondrial metabolism in disease pathogenesis remains to be elucidated. Using an unbiased metabolomic analysis of purified mitochondria, we identified alterations in α-ketoglutarate dehydrogenase (KGDH) pathway upon loss of PD-linked CHCHD2 protein. KGDH, a rate-limiting enzyme complex in the tricarboxylic acid cycle, was decreased in CHCHD2-deficient male mouse brains and human dopaminergic neurons. This deficiency of KGDH led to elevated α-ketoglutarate and increased lipid peroxidation. Treatment of CHCHD2-deficient dopaminergic neurons with lipoic acid, a KGDH cofactor and antioxidant agent, resulted in decreased levels of lipid peroxidation and phosphorylated α-synuclein. CHCHD10, a close homolog of CHCHD2 that is primarily linked to amyotrophic lateral sclerosis/frontotemporal dementia, did not affect the KGDH pathway or lipid peroxidation. Together, these results identify KGDH metabolic pathway as a targetable mitochondrial mechanism for correction of increased lipid peroxidation and α-synuclein in Parkinson's disease.},
}

Animals
*Mitochondria/metabolism/enzymology
*Ketoglutarate Dehydrogenase Complex/metabolism/genetics
Humans
*Lipid Peroxidation/drug effects
*Parkinson Disease/metabolism/genetics/pathology
Male
Mice
Disease Models, Animal
alpha-Synuclein/metabolism
Dopaminergic Neurons/metabolism/drug effects
*Transcription Factors/genetics/metabolism
Mice, Knockout
Thioctic Acid/pharmacology
DNA-Binding Proteins/metabolism/genetics
Brain/metabolism
*Mitochondrial Proteins/metabolism/genetics
Ketoglutaric Acids/metabolism
Mice, Inbred C57BL

@article {pmid40011745,
year = {2025},
author = {Rödström, KEJ and Eymsh, B and Proks, P and Hayre, MS and Cordeiro, S and Mendez-Otalvaro, E and Madry, C and Rowland, A and Kopec, W and Newstead, S and Baukrowitz, T and Schewe, M and Tucker, SJ},
title = {Cryo-EM structure of the human THIK-1 K2P K[+] channel reveals a lower Y gate regulated by lipids and anesthetics.},
journal = {Nature structural & molecular biology},
volume = {32},
number = {7},
pages = {1167-1174},
pmid = {40011745},
issn = {1545-9985},
support = {102161/WT_/Wellcome Trust/United Kingdom ; 215519/WT_/Wellcome Trust/United Kingdom ; MR/W017741/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Cryoelectron Microscopy ; *Potassium Channels, Tandem Pore Domain/chemistry/metabolism/ultrastructure/genetics ; Halothane/pharmacology/chemistry ; Models, Molecular ; Binding Sites ; Ion Channel Gating/drug effects ; *Anesthetics/pharmacology ; Protein Conformation ; },
abstract = {THIK-1 (KCNK13) is a halothane-inhibited and anionic-lipid-activated two-pore domain (K2P) K[+] channel implicated in microglial activation and neuroinflammation, and a current target for the treatment of neurodegenerative disorders, for example Alzheimer's disease and amyothropic lateral sclerosis (ALS). However, compared to other K2P channels, little is known about the structural and functional properties of THIK-1. Here we present a 3.16-Å-resolution cryo-EM structure of human THIK-1 that reveals several distinct features, in particular, a tyrosine in M4 that contributes to a lower 'Y gate' that opens upon activation by physiologically relevant G-protein-coupled receptor and lipid signaling pathways. We demonstrate that linoleic acid bound within a modulatory pocket adjacent to the filter influences channel activity, and that halothane inhibition involves a binding site within the inner cavity, both resulting in conformational changes to the Y gate. Finally, the extracellular cap domain contains positively charged residues that line the ion exit pathway and contribute to the distinct biophysical properties of this channel. Overall, our results provide structural insights into THIK-1 function and identify distinct regulatory sites that expand its potential as a drug target for the modulation of microglial function.},
}

Humans
Cryoelectron Microscopy
*Potassium Channels, Tandem Pore Domain/chemistry/metabolism/ultrastructure/genetics
Halothane/pharmacology/chemistry
Models, Molecular
Binding Sites
Ion Channel Gating/drug effects
*Anesthetics/pharmacology
Protein Conformation

@article {pmid40012174,
year = {2025},
author = {Rajamanickam, G and Hu, Z and Liao, P},
title = {Targeting the TRPM4 Channel for Neurologic Diseases: Opportunity and Challenge.},
journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry},
volume = {31},
number = {5},
pages = {464-482},
doi = {10.1177/10738584251318979},
pmid = {40012174},
issn = {1089-4098},
mesh = {*TRPM Cation Channels/metabolism/antagonists & inhibitors ; Humans ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; },
abstract = {As a monovalent cation channel, the transient receptor potential melastatin 4 (TRPM4) channel is a unique member of the transient receptor potential family. Abnormal TRPM4 activity has been identified in various neurologic disorders, such as stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, pathologic pain, and epilepsy. Following brain hypoxia/ischemia and inflammation, TRPM4 up-regulation and enhanced activity contribute to the cell death of neurons, vascular endothelial cells, and astrocytes. Enhanced ionic influx via TRPM4 leads to cell volume increase and oncosis. Depolarization of membrane potential following TRPM4 activation and interaction between TRPM4 and N-methyl-d-aspartate receptors exacerbate excitotoxicity during hypoxia. Importantly, TRPM4 expression and activity remain low in healthy neurons, making it an ideal drug target. Current approaches to inhibit or modulate the TRPM4 channel have various limitations that hamper the interpretation of TRPM4 physiology in the nervous system and potentially hinder their translation into therapy. In this review, we discuss the pathophysiologic roles of TRPM4 and the different inhibitors that modulate TRPM4 activity for potential treatment of neurologic diseases.},
}

*TRPM Cation Channels/metabolism/antagonists & inhibitors
Humans
*Nervous System Diseases/metabolism/drug therapy
Animals

@article {pmid40017137,
year = {2025},
author = {Lovett, A and Chary, S and Babu, S and Bruneteau, G and Glass, JD and Karlsborg, M and Ladha, S and Mayl, K and McDermott, C and Bucelli, RC and Chiò, A and Ferguson, TA and Cochrane, T and Fradette, S and Smirnakis, K and Inra, J and Malek, S and Fanning, L},
title = {Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {71},
number = {6},
pages = {1006-1015},
pmid = {40017137},
issn = {1097-4598},
support = {//Biogen/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Middle Aged ; Male ; Female ; *Oligonucleotides/adverse effects/therapeutic use ; Adult ; Aged ; Superoxide Dismutase-1/genetics ; Myelitis/chemically induced ; Papilledema/chemically induced ; },
abstract = {INTRODUCTION/AIMS: Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations (SOD1-ALS). Here we report serious neurologic adverse events (AEs) that occurred in the tofersen clinical trials in people with SOD1-ALS.

METHODS: Serious neurologic AEs of myelitis, radiculitis, aseptic meningitis, and papilledema reported in the tofersen clinical trials are described. Serious AEs were defined according to International Conference for Harmonization guidelines, and neurologic AEs in clinical trials were diagnosed by investigators based on symptoms, clinical examination findings, and diagnostic workup.

RESULTS: Ten participants (approximately 7% of tofersen 100-mg-treated trial participants) experienced a total of 12 serious neurologic AEs-4 of myelitis, 2 of radiculitis, 2 of aseptic meningitis, and 4 of intracranial hypertension (ICH) and/or papilledema. All events but one resolved either spontaneously, with dosing interruption/modification, or with concomitant therapies. One event was ongoing but improved as of December 2022. While 3 events led to tofersen treatment discontinuation, all other participants were able to remain on treatment. No event was life-threatening or fatal.

DISCUSSION: Some antisense oligonucleotides (ASOs) have been described as having pro-inflammatory properties. Aseptic meningitis has been reported with nusinersen; however, myelitis, radiculitis, increased intracranial pressure, and papilledema have not been reported with ASO treatment. These neurologic AEs should be considered when assessing the overall benefit/risk of tofersen treatment for SOD1-ALS. Safety data from the open-label extension and expanded access program will continue to characterize these events and further inform the safety profile of tofersen in SOD1-ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/genetics
Middle Aged
Male
Female
*Oligonucleotides/adverse effects/therapeutic use
Adult
Aged
Superoxide Dismutase-1/genetics
Myelitis/chemically induced
Papilledema/chemically induced

@article {pmid40019593,
year = {2025},
author = {Dobroniak, CC and Lesche, V and Olgemöller, U and Beck, P and Lehmann, W and Spering, C},
title = {Surgical strategy for chest wall reconstruction secondary to cardiopulmonary resuscitation versus post-traumatic.},
journal = {European journal of trauma and emergency surgery : official publication of the European Trauma Society},
volume = {51},
number = {1},
pages = {122},
pmid = {40019593},
issn = {1863-9941},
mesh = {Humans ; *Cardiopulmonary Resuscitation/adverse effects ; Male ; *Flail Chest/surgery/etiology ; Female ; Middle Aged ; Retrospective Studies ; *Thoracic Wall/surgery ; *Rib Fractures/surgery ; Sternum/injuries/surgery ; Adult ; *Plastic Surgery Procedures/methods ; *Fracture Fixation, Internal/methods ; Aged ; Length of Stay/statistics & numerical data ; *Thoracic Injuries/surgery ; Germany ; Bone Plates ; Treatment Outcome ; },
abstract = {PURPOSE: In mechanically cardiopulmonary resuscitated (CPR) patients, chest compressions at the level of the 3rd to 5th rib on the sternum result in reproducibly similar injury patterns: parasternal osteochondral dissociation (OCS) on both sides in combination with a sternal fracture with or without an additional serial rib fracture in the anterolateral column (ALS). This injury biomechanically impairs physiological breathing, resulting in an inverse breathing pattern. Trauma patients, on the other hand, often show a mixed pattern depending on the location of the main energy. The aim of the study was to evaluate the surgical technique of chest wall reconstruction (CWR) using transsternal refixation of the 5th rib on both sides in combination with plate osteosynthesis of the sternum and to analyze its success in comparison to the surgical strategy of CWR in the context of a traumatic genesis.

METHOD: Data acquisition was performed using medical records of a Level I Trauma Centre in Germany and compare patients with radiologically or clinically diagnosed flail chest as a result of cardiopulmonary mechanical resuscitation (CPR). The retrospective study included patients in the period 2018-2023 after surgical CWR. The patients were either post-CPR (n = 29; CPR) or trauma patients (n = 36; trauma). The collective was described and analyzed using the digital patient file, as well as data on ICU stay and duration of ventilation or conversion to assisted ventilation modes, reason for chest wall instability, time of surgery, length of stay and mortality. As a long-term follow-up, body plethysmography was analyzed comparatively. Primary endpoints were mean length of stay in ICU, time to surgery, ventilator dependency and mortality rate. Secondary endpoints were time to transfer to rehabilitation, ventilation disorders and long term outcome.

RESULTS: In the period 65 patients (48 m, 17w) were included, 29 of whom had been mechanically resuscitated (CPR), 36 formed to post-traumatic cohort (trauma). The CPR were significantly older (69 vs. 58 years; p-value 0.003). The duration from CPR to surgery was on average significantly longer than trauma to surgery (16.76 vs. 4.11 days). The mean length of stay in ICU were 30 days (trauma) and 45 days for CPR (significantly longer, p-value 0.0008). The mean duration of ventilation was 188 h for trauma and 593 h for CPR. Extubation or conversion to assisted, relevant de-escalating ventilation modes was possible in both groups after a mean of 38 h post-OP. Among the CPR patients, 4 died in hospital (hospital mortality: CPR 20.7% vs. trauma 5.6%), 7 (30%) were transferred to an early clinical rehabilitation and 10 were discharged to home or follow-up treatment. In the case of trauma, 5 (14.7%) were transferred to an early clinical rehabilitation and 20 were discharged to home or follow-up treatment. Bodyplethysmography 6 months after CPR / trauma showed no differences in both collectives with regard to ventilation disorders. Diffusion was prolonged in both groups, presumably due to the healing process of lungs contusion. Both showed no restriction disorders.

CONCLUSION: Chest wall reconstruction, including plate osteosynthesis of the sternum in combination with transsternal fixation of the 5th rib on both sides can largely restore physiological respiratory mechanics immediately after surgery and accelerate the weaning success. In the management of patients after CPR, the initial diagnosis which had indicated resuscitation, is the main focus and can often be an obstacle to extubation. Nevertheless, independent breathing can be accelerated by restoring the biomechanics through early surgical treatment using CWR and saves long-term ICU stays with the potential for further complication and resource consumption. CWR forms the essential basis for early rehabilitation of the underlying cause of resuscitation. Ventilation disorders do not occur after surgical CWR, even during the course of the procedure.},
}

Humans
*Cardiopulmonary Resuscitation/adverse effects
Male
*Flail Chest/surgery/etiology
Female
Middle Aged
Retrospective Studies
*Thoracic Wall/surgery
*Rib Fractures/surgery
Sternum/injuries/surgery
Adult
*Plastic Surgery Procedures/methods
*Fracture Fixation, Internal/methods
Aged
Length of Stay/statistics & numerical data
*Thoracic Injuries/surgery
Germany
Bone Plates
Treatment Outcome

@article {pmid40024955,
year = {2025},
author = {Masood, S and Almas, MS and Hassan, SSU and Tahira, S and Fiaz, MH and Minhas, UEA and Zafar, HMQ and Masood, M},
title = {Safety and efficacy of arimoclomol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {46},
number = {7},
pages = {2985-2994},
pmid = {40024955},
issn = {1590-3478},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Randomized Controlled Trials as Topic ; *Neuroprotective Agents/adverse effects/therapeutic use ; Treatment Outcome ; Hydroxylamines ; },
abstract = {OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) is a debilitating motor neuron disorder characterized by muscle weakness, atrophy, and spasticity. This meta-analysis aims to assess the safety and efficacy of Arimoclomol in patients with ALS.

METHOD: A comprehensive literature search was conducted on 3 databases to discover articles published up to August 2024. Included studies were randomized controlled trials (RCTs). Data was analysed using Review Manager (v5.4). Cochrane Risk of Bias-2 (RoB-2) was adopted to assess the quality of RCTs.

RESULTS: A total of 359 patients were analysed, with 239 individuals in the Arimoclomol group and 120 individuals in the placebo group. The pooled analysis of the primary outcome, change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score from baseline, did not demonstrate a statistically significant difference favoring the Arimoclomol group (MD = 0.4495; 95% CI: -0.39, 1.27; p = 0.30). Similarly, secondary outcomes, including the Combined Assessment of Function and Survival (CAFS) rank score (MD = 1.00; 95% CI: -2.68, 4.67; p = 0.60), increase in transaminases (RR = 1.05; 95% CI: 0.19, 5.70; p = 0.95), mortality rate (RR = 0.86; 95% CI: 0.55, 1.34; p = 0.50), and adverse events (RR = 0.86; 95% CI: 0.55, 1.34; p = 0.50), showed no statistically significant differences between the groups.

CONCLUSION: This study does not conclusively demonstrate that Arimoclomol has beneficial effects on ALS patients' physical functionality but shows promise for safety. Further clinical trials are needed to explore the neuroprotective effects of Arimoclomol in the treatment of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
Randomized Controlled Trials as Topic
*Neuroprotective Agents/adverse effects/therapeutic use
Treatment Outcome
Hydroxylamines

@article {pmid40025240,
year = {2025},
author = {Maier, A and Kettemann, D and Weyen, U and Grehl, T and Schulte, PC and Steinbach, R and Rödiger, A and Weydt, P and Petri, S and Wolf, J and Grosskreutz, J and Koch, JC and Weishaupt, JH and Rosseau, S and Norden, J and Körtvélyessy, P and Koch, B and Holm, T and Hildebrandt, B and Schumann, P and Walter, B and Riitano, A and Münch, C and Meyer, T and Spittel, S},
title = {Provision, cough efficacy and treatment satisfaction of mechanical insufflation-exsufflation in a large multicenter cohort of patients with amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {7360},
pmid = {40025240},
issn = {2045-2322},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology ; *Cough/therapy/etiology ; Male ; Female ; Middle Aged ; *Insufflation/methods ; Aged ; *Patient Satisfaction ; Treatment Outcome ; Longitudinal Studies ; Germany ; Adult ; },
abstract = {In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited systematic research on MI-E provision, symptom alleviation, or patient satisfaction. The research platform Ambulanzpartner coordinated this longitudinal observational study conducted in 12 German ALS centers from July 2018 to September 2023. Patients were enrolled based on ALS-related cough deficiency requiring MI-E therapy. The study recorded provision, reasons for withholding MI-E, clinical parameters, therapy frequency, subjective cough deficiency, and symptomatic relief. Satisfaction with MI-E therapy was determined by the likelihood of recommendation. Out of 694 ALS patients indicated for MI-E, 527 (75.9%) received the therapy. The primary reason for non-provision was that the patient had died before provision (n = 66 of 167; 39.5%). These patients were significantly more affected as represented by higher progression rates and lower cough peak flows (CPF) at the time of MI-E indication (p < 0.05). Most patients who received MI-E used it daily (n = 290 of 370; 78.4%). Self-assessed cough deficiency correlated with clinical measurements, especially for patients with higher deficits. At follow-up visits, patients reported reduced cough deficiency (p < 0.001). Frequent MI-E use was linked to greater symptom relief and higher likelihood of recommending the therapy. This study highlights the symptomatic and palliative potential of MI-E therapy for ALS patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology
*Cough/therapy/etiology
Male
Female
Middle Aged
*Insufflation/methods
Aged
*Patient Satisfaction
Treatment Outcome
Longitudinal Studies
Germany
Adult

@article {pmid40027570,
year = {2025},
author = {Giorgio, A and Ciracì, E and De Luca, M and Stella, G and Giorgio, V},
title = {Hepatic abscess and hydatid liver cyst: European infectious disease point of view.},
journal = {World journal of hepatology},
volume = {17},
number = {2},
pages = {103325},
pmid = {40027570},
issn = {1948-5182},
abstract = {This manuscript is based on a recent study by Pillay et al that was published in recently. Liver abscesses can be caused by rare potentially life-threatening infections of either bacterial or parasitic origin. The incidence rate in Europe is lower than in developing countries, but it is a major complication with high morbidity, particularly in immunocompromised patients. They are most frequently caused by Enterobacterales infections, but hypervirulent Klebsiella strains are an emerging problem in Western countries. Amoebiasis has been a public health problem in Europe, primarily imported from other endemic foci. At the same time, this infection is becoming an emerging disease, as the number of infected patients who have not traveled to endemic areas is rising. Treatment options for hydatid liver cyst include chemotherapy, open or laparoscopic surgery, percutaneous treatment (percutaneous aspiration, re-aspiration and injection and its modification) and ''wait and watch'' strategy. Most hydatid liver cyst patients in Pillay et al's study received surgical treatment, but several studies have confirmed the safety and efficacy of percutaneous aspiration, re-aspiration and injection.},
}

@article {pmid40029136,
year = {2025},
author = {Revi, N and Nandeshwar, M and Harijan, D and Sankaranarayanan, SA and Joshi, M and Prabusankar, G and Rengan, AK},
title = {Acridine Benzimidazolium Derivatives Induced Protective Microglia Polarization and In Silico TDP-43 Interaction─Potential Implications for Amyotrophic Lateral Sclerosis.},
journal = {ACS chemical neuroscience},
volume = {16},
number = {6},
pages = {1103-1116},
doi = {10.1021/acschemneuro.4c00791},
pmid = {40029136},
issn = {1948-7193},
mesh = {*Microglia/drug effects/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Animals ; *DNA-Binding Proteins/metabolism/antagonists & inhibitors ; Humans ; Mice ; *Acridines/pharmacology/chemistry ; *Benzimidazoles/pharmacology/chemistry ; Molecular Docking Simulation ; *Neuroprotective Agents/pharmacology ; Cell Polarity/drug effects ; },
abstract = {Abnormal protein aggregation and associated neuronal-glial cell cytotoxicity lead to a plethora of neurodegenerative disorders. Most of the earlier investigations on understanding neurodegenerative disease progression and cure focused on neuronal damage and restoration potential. With increased evidence on the role of glial cells like microglia and astrocytes in mediating these disorders, more studies are dedicated to understanding the role of inflammatory responses mediated by glial cells and how they lead to neuroinflammation. Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder caused by TDP-43 aggregation that affects motor neurons. Pro-inflammatory microglia are considered to aggravate the disorder condition. In the current study, a previously reported molecule with TDP-43 inhibition, 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl)imidazol-3-ium) dibromide salt (AIM4), is analyzed for its microglia polarization properties along with two other derivatives, 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(2-ethoxy-2-oxoethyl)benzimidazol-3-ium) dibromide salt (ABE) and 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl)benzoimidazol-3-ium) dibromide salt (ABA). The 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(2-ethoxy-2-oxoethyl)benzimidazol-3-ium) dibromide salt (ABE) and 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl) benzimidazol-3-ium) dibromide salt (ABA) display the increased ability to maintain microglial cells to anti-inflammatory state and TDP-43 binding as compared to 3,3'-(acridine-4,5-diylbis(methylene)) bis(carboxymethyl)imidazolium dibromide salt (AIM4). This was confirmed from total nitrite levels, mitochondria membrane potential analysis, and molecular docking studies. The selected pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) displayed decreased levels, and anti-inflammatory cytokines IL-4 and IL-10 displayed increased levels, however not very significantly, upon treatment with all acridine derivatives. The compounds were investigated on lipopolysaccharides (LPS)-triggered mouse microglial cells and Danio rerio embryos displaying no significant cytotoxicity and physiological changes (cardiac rhythm), respectively. In molecular docking studies, alanine at 315 mutated to glutamate of TDP-43 directly interacts with AIM4. However, π-σ interactions of the aromatic backbone of acridine in ABE and ABA with 313 phenylalanine of TDP-43 along with hydrogen bonds formed between 309, 310 glycine amino acids and imidazolium bromide side chains rendered a stronger binding of these acridine derivatives with the protein potentially inhibiting fibrillation. Conclusion: ABA, ABE, and AIM4 maintain microglia in an anti-inflammatory state. However, more studies are required to understand its interaction with TDP-43 and the mechanism of its anti-inflammatory nature.},
}

*Microglia/drug effects/metabolism
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy
Animals
*DNA-Binding Proteins/metabolism/antagonists & inhibitors
Humans
Mice
*Acridines/pharmacology/chemistry
*Benzimidazoles/pharmacology/chemistry
Molecular Docking Simulation
*Neuroprotective Agents/pharmacology
Cell Polarity/drug effects

@article {pmid40030015,
year = {2025},
author = {Johnson, EA and Nowar, R and Viola, KL and Huang, W and Zhou, S and Bicca, MA and Zhu, W and Kranz, DL and Klein, WL and Silverman, RB},
title = {Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {10},
pages = {e2402117122},
pmid = {40030015},
issn = {1091-6490},
support = {AG061708//HHS | National Institutes of Health (NIH)/ ; S10 OD032367/OD/NIH HHS/United States ; R56 AG050492/AG/NIA NIH HHS/United States ; R01 AG061708/AG/NIA NIH HHS/United States ; AG050492//HHS | National Institutes of Health (NIH)/ ; },
mesh = {*Amyloid beta-Peptides/metabolism ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Neurons/metabolism/drug effects ; Hippocampus/metabolism/drug effects ; Mice ; Autophagy/drug effects ; Protein Aggregation, Pathological/drug therapy/metabolism ; Alzheimer Disease/metabolism/drug therapy ; Lysosomes/metabolism ; Protein Aggregates/drug effects ; },
abstract = {Protein aggregation is a hallmark of neurodegenerative diseases, which connects these neuropathologies by a common phenotype. Various proteins and peptides form aggregates that are poorly degraded, and their ensuing pathological accumulation underlies these neurodegenerative diseases. Similarities may exist in the mechanisms responsible for the buildup of these aggregates. Therefore, therapeutics designed to treat one neurodegenerative disease may be beneficial to others. In ALS models, the compound NU-9 was previously shown to block neurodegeneration produced by aggregation-inducing mutations of SOD-1 and TDP-43 [B. Genç et al., Clin. Transl. Med. 11, e336 (2021)]. Here, we report that NU-9 also prevents the accumulation of amyloid beta oligomers (AβOs), small peptide aggregates that are instigators of Alzheimer's disease neurodegeneration [M. Tolar et al., Int. J. Mol. Sci. 22, 6355 (2021)]. AβO buildup was measured by immunofluorescence imaging of cultured hippocampal neurons exposed to exogenous monomeric Aβ. In this model, AβO buildup occurs via cathepsin L- and dynamin-dependent trafficking. This is prevented by NU-9 through a cellular mechanism that is cathepsin B- and lysosome-dependent, suggesting that NU-9 enhances the ability of endolysosomal trafficking to protect against AβO buildup. This possibility is strongly supported by a quantitative assay for autophagosomes that shows robust stimulation by NU-9. These results contribute additional understanding to the mechanisms of protein aggregation and suggest that multiple neurodegenerative diseases might be treatable by targeting common pathogenic mechanisms responsible for protein aggregation.},
}

*Amyloid beta-Peptides/metabolism
Humans
Animals
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
Neurons/metabolism/drug effects
Hippocampus/metabolism/drug effects
Mice
Autophagy/drug effects
Protein Aggregation, Pathological/drug therapy/metabolism
Alzheimer Disease/metabolism/drug therapy
Lysosomes/metabolism
Protein Aggregates/drug effects

@article {pmid40030850,
year = {2025},
author = {Hong, Z and Yi, S and Deng, M and Zhong, Y and Zhao, Y and Li, L and Zhou, H and Xiao, Y and Hu, X and Niu, L},
title = {Transcranial Focused Ultrasound Modifies Disease Progression in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis.},
journal = {IEEE transactions on ultrasonics, ferroelectrics, and frequency control},
volume = {72},
number = {2},
pages = {191-201},
doi = {10.1109/TUFFC.2024.3525143},
pmid = {40030850},
issn = {1525-8955},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology/diagnostic imaging/genetics ; Mice ; Disease Models, Animal ; Mice, Transgenic ; *Ultrasonic Therapy/methods ; Superoxide Dismutase-1/genetics ; Disease Progression ; Muscle, Skeletal/physiopathology ; Male ; Motor Cortex ; Humans ; Elasticity Imaging Techniques ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressively worsening neurodegenerative condition with very few treatment options available. Ultrasound neuromodulation offers promising benefits for treating neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. However, the effects and underlying mechanisms of ultrasound neuromodulation on ALS remain unclear. A head-mounted ultrasound neuromodulation system was developed to noninvasively stimulate the motor cortex of symptomatic mice carrying the G93A human SOD1 mutation (SOD $1^{\text {G93A}}
$) for four weeks. Motor performance was assessed through the rotarod locomotor test, grip strength test, and open field test. In addition, the effect of ultrasound stimulation on the elastic modulus of gastrocnemius muscle atrophy was measured using real-time shear wave elastography (SWE). Subsequently, the brain tissues of the mice were harvested. Gastrocnemius morphology was examined using hematoxylin-eosin and Gomori aldehyde-fuchsin (GAF) staining. The number of neurons and the phenotype of microglia in the motor cortex were observed by immunohistochemical analysis. Ultrasound therapy delayed disease onset by 10.7% and increased the lifespan by 6.7% in SOD $1^{\text {G93A}}
$ mice by reduction of neuronal loss and enhancement of M2 microglia in the motor cortex. Furthermore, we found significant improvements in motor function for ultrasound-treated mice. More importantly, ultrasound stimulation ameliorated gastrocnemius muscle atrophy in the SOD $1^{\text {G93A}}
$ mice. These results revealed the neuroprotective effects of ultrasound against the disease pathogenesis of SOD $1^{\text {G93A}}
$ mice. Transcranial ultrasound neuromodulation provides an innovative tool for the intervention and treatment of neurodegenerative diseases.},
}

Animals
*Amyotrophic Lateral Sclerosis/therapy/physiopathology/diagnostic imaging/genetics
Mice
Disease Models, Animal
Mice, Transgenic
*Ultrasonic Therapy/methods
Superoxide Dismutase-1/genetics
Disease Progression
Muscle, Skeletal/physiopathology
Male
Motor Cortex
Humans
Elasticity Imaging Techniques

@article {pmid40032170,
year = {2025},
author = {Placidi, E and Fionda, B and Rosa, E and Tagliaferri, L and De Spirito, M},
title = {Commentary on feliciani Giacomo et al.'s study of comparison of HDR-brachytherapy and tomotherapy for the treatment of non-melanoma skin cancers of the head and neck.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {206},
number = {},
pages = {110826},
doi = {10.1016/j.radonc.2025.110826},
pmid = {40032170},
issn = {1879-0887},
}

@article {pmid40033250,
year = {2025},
author = {Lu, C and Huang, XX and Huang, M and Liu, C and Xu, J},
title = {Mendelian randomization of plasma proteomics identifies novel ALS-associated proteins and their GO enrichment and KEGG pathway analyses.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {82},
pmid = {40033250},
issn = {1471-2377},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Mendelian Randomization Analysis/methods ; *Proteomics/methods ; Genome-Wide Association Study ; *Blood Proteins/genetics/metabolism ; Biomarkers/blood ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disorder with an increasing incidence rate. Despite advances in ALS research over the years, the precise etiology and pathogenic mechanisms remain largely elusive.

OBJECTIVE: To identify novel plasma proteins associated with ALS through Mendelian randomization methods in large-scale plasma proteomics and to provide potential biomarkers and therapeutic targets for ALS treatment.

METHODS: This study employed a large-scale plasma proteomic Mendelian randomization approach using genetic data from 80,610 individuals of European ancestry (including 20,806 ALS patients and 59,804 controls) derived from a genome-wide association study (GWAS). Protein quantitative trait loci (pQTLs) data were obtained from Ferkingstad et al. (2021), which measured 4,907 proteins in 35,559 Icelandic individuals. Multiple Mendelian randomization (MR) techniques were utilized, including weighted median, MR-Egger, Wald ratio, inverse-variance weighting (IVW), basic model, and weighted model. Heterogeneity was evaluated using Cochran's Q test. Horizontal pleiotropy was assessed through the MR-Egger intercept test and MR-PRESSO outlier detection. Sensitivity analysis was performed via leave-one-out analysis.

RESULTS: MR analysis revealed potential causal associations between 491 plasma proteins and ALS, identifying 19 novel plasma proteins significantly linked to the disease. Proteins such as C1QC, UMOD, SLITRK5, ASAP2, TREML2, DAPK2, ARHGEF10, POLM, SST, and SIGLEC1 showed positive correlations with ALS risk, whereas ADPGK, BTNL9, COLEC12, ADGRF5, FAIM, CRTAM, PRSS3, BAG5, and PSMD11 exhibited negative correlations. Reverse MR analyses confirmed that ALS negatively correlates with ADPGK and ADGRF5 expression. Enrichment analyses, including Gene Ontology (GO) functional analysis, indicated involvement in critical biological processes such as external encapsulating structure organization, extracellular matrix organization, chemotaxis, and taxis. KEGG pathway analysis highlighted significant enrichment in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interactions, and axon guidance.

CONCLUSION: This study enhances the understanding of ALS pathophysiology and proposes potential biomarkers and mechanistic insights for therapeutic development. Future research should explore the clinical translation of these findings to improve ALS patient outcomes and quality of life.},
}

*Amyotrophic Lateral Sclerosis/genetics/blood
Humans
*Mendelian Randomization Analysis/methods
*Proteomics/methods
Genome-Wide Association Study
*Blood Proteins/genetics/metabolism
Biomarkers/blood

@article {pmid40035928,
year = {2025},
author = {Amos, J and Moase, J and Sladeczek, IE},
title = {A scoping review of school-based expressive writing implementation reporting practices: missed opportunities and new research directions.},
journal = {Discover mental health},
volume = {5},
number = {1},
pages = {27},
pmid = {40035928},
issn = {2731-4383},
abstract = {BACKGROUND: Expressive writing (EW) interventions are an effective, flexible, and cost-efficient option for mental health promotion, making them ideally suited for resource-limited school settings. However, the effectiveness of EW interventions varies greatly across studies, which may be partly explained by how EW interventions are implemented. As school-based EW interventions become increasingly popular and more widely used, rigorous reporting of implementation can help advance this emerging field by informing how variation in implementation across studies influences intervention outcomes.

PURPOSE: The purpose of this scoping review was to evaluate the implementation reporting practices of EW interventions in school settings as they can profoundly impact EW effectiveness.

METHODS: The present scoping review assessed the current state of fidelity of implementation (implementation) reporting in the school-based EW literature and identified areas where more rigorous reporting is needed. Out of an initial sample of 367 studies, 19 were eligible for inclusion in the review. Data were analyzed for critical issues and themes derived from Cargo et al.'s (2015) Checklist for Implementation (Ch-IMP).

RESULTS: Overall, the results of this scoping review indicate that researchers who implement EW in school settings have not consistently assessed key implementation domains such as dose received and fidelity.

CONCLUSIONS: To address this problem, the present review adds a unique contribution to the literature by identifying how rigorous reporting of implementation can strengthen the evidence base for school-based EW interventions. Specifically, researchers can support the use of EW interventions in schools through increased implementation reporting to better understand how variability in fidelity of implementation affects treatment outcomes.},
}

@article {pmid40038221,
year = {2025},
author = {Mustafa, F and Mittal, S and Garg, D and Agarwal, A and Garg, A and Gupta, BK and Soneja, M and Srivastava, AK},
title = {HIV associated motor neuron disease (MND): A case series with systematic review of literature.},
journal = {Journal of neurovirology},
volume = {31},
number = {1},
pages = {1-15},
pmid = {40038221},
issn = {1538-2443},
mesh = {Humans ; *HIV Infections/drug therapy/complications/virology ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/virology/drug therapy/diagnostic imaging/pathology ; Female ; Adult ; *Motor Neuron Disease/virology/drug therapy ; Viral Load ; CD4 Lymphocyte Count ; Anti-HIV Agents/therapeutic use ; },
abstract = {Human immunodeficiency virus (HIV) associated motor neuron disease (MND) is very rare. HIV infection can cause an MND-like syndrome due to central nervous system (CNS) involvement de novo or during antiretroviral therapy (ART) due to CNS escape. We present two cases: one with a classic amyotrophic lateral sclerosis (ALS) phenotype, which was the manifestation of symptomatic CNS escape from ART, and the second with a primary lateral sclerosis (PLS) phenotype associated with underlying HIV infection. A systematic review of published literature of people living with HIV (PLHIV) who developed ALS/ MND was conducted using the PubMed, Embase, and Lilacs databases. A total of 91 cases were found, 89 of which were obtained from 37 articles, and two were included from our own case series. In patients with HIV-associated MND, 63 patients reviewed had a classic ALS phenotype followed by progressive muscular atrophy variant (12), progressive bulbar palsy (8), PLS (7) and bulbar onset ALS (1). Neuroimaging, electrophysiology, cerebrospinal fluid (CSF) analysis, CSF and serum HIV viral load, and CD4 count investigations were used for diagnosis. Following the initiation or modification of antiretroviral therapy (ART), approximately 70% exhibited an improvement or a stable disease course. HIV-associated MND is a rare condition that can occur in both ART-naive individuals and those on treatment. A proportion of cases (~ 70%) show improvement with ART. Accurate diagnosis requires the exclusion of opportunistic infections, which remains a critical yet challenging aspect of managing this condition.},
}

Humans
*HIV Infections/drug therapy/complications/virology
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/virology/drug therapy/diagnostic imaging/pathology
Female
Adult
*Motor Neuron Disease/virology/drug therapy
Viral Load
CD4 Lymphocyte Count
Anti-HIV Agents/therapeutic use

@article {pmid40041912,
year = {2025},
author = {Dash, UC and Bhol, NK and Swain, SK and Samal, RR and Nayak, PK and Raina, V and Panda, SK and Kerry, RG and Duttaroy, AK and Jena, AB},
title = {Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications.},
journal = {Acta pharmaceutica Sinica. B},
volume = {15},
number = {1},
pages = {15-34},
pmid = {40041912},
issn = {2211-3835},
abstract = {Neuroprotection is a proactive approach to safeguarding the nervous system, including the brain, spinal cord, and peripheral nerves, by preventing or limiting damage to nerve cells and other components. It primarily defends the central nervous system against injury from acute and progressive neurodegenerative disorders. Oxidative stress, an imbalance between the body's natural defense mechanisms and the generation of reactive oxygen species, is crucial in developing neurological disorders. Due to its high metabolic rate and oxygen consumption, the brain is particularly vulnerable to oxidative stress. Excessive ROS damages the essential biomolecules, leading to cellular malfunction and neurodegeneration. Several neurological disorders, including Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke, are associated with oxidative stress. Understanding the impact of oxidative stress in these conditions is crucial for developing new treatment methods. Researchers are exploring using antioxidants and other molecules to mitigate oxidative stress, aiming to prevent or slow down the progression of brain diseases. By understanding the intricate interplay between oxidative stress and neurological disorders, scientists hope to pave the way for innovative therapeutic and preventive approaches, ultimately improving individuals' living standards.},
}

@article {pmid40044193,
year = {2025},
author = {Ross, WT and Buday, S and Yakel, E and Khabele, D and Balls-Berry, J and As-Sanie, S and Colditz, G and Baumann, AA},
title = {Does interdisciplinary group care for the treatment of endometriosis improve pain interference: protocol for a pilot randomised controlled trial at an urban academic medical centre.},
journal = {BMJ open},
volume = {15},
number = {3},
pages = {e097372},
pmid = {40044193},
issn = {2044-6055},
support = {K23 HD110710/HD/NICHD NIH HHS/United States ; KL2 TR002346/TR/NCATS NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; Academic Medical Centers ; *Chronic Pain/therapy/etiology ; *Endometriosis/therapy/complications ; *Pain Management/methods ; Pain Measurement ; *Patient Care Team ; *Pelvic Pain/therapy/etiology ; Pilot Projects ; Quality of Life ; Randomized Controlled Trials as Topic ; },
abstract = {INTRODUCTION: Endometriosis affects 10-15% of people assigned female at birth and can cause chronic pelvic pain and impair many domains of quality of life, such as fertility, mood and bladder, bowel and sexual function. Current treatments often fail, leading to recurrent pain and the need for reintervention. As endometriosis negatively affects many domains of life, a variety of non-pharmacological treatments modestly improve symptoms. To bundle these interventions into accessible packaging, our interdisciplinary team developed a novel endometriosis intervention titled 'Peer-Empowered Endometriosis Pain Support (PEEPS)', an 8-week integrative group care intervention. Here, we present the protocol for a pilot randomised controlled trial (RCT) to evaluate the effectiveness and implementation of PEEPS for people with endometriosis-associated pain refractory to surgical management. We hypothesise that patients who complete the PEEPS programme will show a greater decrease in pain interference in daily activities at intervention completion as compared with baseline than those in the education arm.

METHODS AND ANALYSIS: This is a hybrid type 1 effectiveness-implementation mixed-methods RCT in which 60 participants will be randomised using computer-generated random numbers stratified by group in the ratio 1:1 to PEEPS plus usual versus educational handout plus usual care. The primary outcome is change in pain interference from baseline to intervention completion. Secondary outcomes include change in pain interference from baseline to 6 months and 12 months postintervention, as well as change in other quality-of-life measures as measured by nine validated questionnaires from baseline to completion, 6 months and 12 months. Proctor et al's Implementation Outcomes Framework will be used to evaluate acceptability, appropriateness and feasibility of PEEPS implementation, and the Consolidated Framework for Implementation Research will be used to guide the evaluation of barriers and facilitators of PEEPS at the patient and provider levels. Primary data analyses will follow the intention-to-treat principle. Descriptive statistics and two-sample t-tests for normally distributed values and Wilcoxon Rank-Sum test were performed for non-normally distributed values. Frequency analysis and Fisher's exact or χ[2] tests will be used for categoric variables as appropriate. Longitudinal analysis of the primary and secondary outcomes will be conducted with a mixed-effects model to investigate the effect of PEEPS compared with education. Least square means (LSMs) and the corresponding 95% CIs at each timepoint, as well as LSM differences and 95% CIs between any post-baseline and baseline will be provided for the outcomes. ORs and 95% CIs will be calculated for categorical outcomes. Qualitative data will be collected in the form of open-ended feedback, focus groups with programme completers and semistructured interviews with participants who complete two or fewer sessions. The analysis will use an embedded design-experimental model in which quantitative and qualitative outcomes will occur concurrently with weight priority given to quantitative data.

ETHICS AND DISSEMINATION: This trial was approved by the Washington University in St. Louis Institutional Review Board (protocol 202402082) on 27 March 2024 and has low risk of harm to participants. All deidentified data from this project will be shared via Digital Commons@Becker. The findings of this study will be disseminated via scientific meetings and peer-reviewed journals. The results and conclusions will be summarised for patients and the public in common language using infographics to make the findings accessible. This pilot RCT will yield the effect size for PEEPS and generate implementation context and outcomes data to guide PEEPS application to real-world practice. If PEEPS proves to be effective, this study will inform adaptation and scaling to improve the lives of people with endometriosis through a non-hormonal, fertility-preserving approach.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov; NCT06549985.},
}

Adult
Female
Humans
Academic Medical Centers
*Chronic Pain/therapy/etiology
*Endometriosis/therapy/complications
*Pain Management/methods
Pain Measurement
*Patient Care Team
*Pelvic Pain/therapy/etiology
Pilot Projects
Quality of Life
Randomized Controlled Trials as Topic

@article {pmid40056503,
year = {2025},
author = {Zhan, A and Zhong, K and Zhang, K},
title = {Novel subcellular regulatory mechanisms of protein homeostasis and its implications in amyotrophic lateral sclerosis.},
journal = {Biochemical and biophysical research communications},
volume = {756},
number = {},
pages = {151582},
doi = {10.1016/j.bbrc.2025.151582},
pmid = {40056503},
issn = {1090-2104},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Proteostasis ; Animals ; Homeostasis ; Mitochondria/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disorder. Protein aggregates induce various forms of neuronal dysfunction and represent pathological hallmarks in ALS patients. Reducing protein aggregates could be a promising therapeutic strategy for ALS. While most studies have focused on cytoplasmic protein homeostasis, neurons adaptively reduce aggregates across subcellular compartments during stress through previously uncharacterized mechanisms. Here, we summarize novel compartment-specific proteostatic mechanisms: (1) the ERAD/RESET pathways, (2) HSPs-mediated nuclear sequestration, (3) mitochondrial aggregate import (MAGIC), (4) neurite-localized UPS/autophagosome and NMP, and (5) exopher-mediated extracellular disposal. These mechanisms collectively ensure cellular stress adaptation and provide novel therapeutic targets for ALS treatment.},
}

*Amyotrophic Lateral Sclerosis/metabolism/pathology
Humans
*Proteostasis
Animals
Homeostasis
Mitochondria/metabolism

@article {pmid40057669,
year = {2025},
author = {Hatcher, H and Stankeviciute, S and Learn, C and Qu, AX},
title = {Regulatory, Translational, and Operational Considerations for the Incorporation of Biomarkers in Drug Development.},
journal = {Therapeutic innovation & regulatory science},
volume = {59},
number = {3},
pages = {519-526},
pmid = {40057669},
issn = {2168-4804},
mesh = {*Drug Development/legislation & jurisprudence ; Humans ; *Biomarkers ; United States ; United States Food and Drug Administration ; Drug Approval ; },
abstract = {BACKGROUND: Biomarkers are an integral component in the drug development paradigm. According to the US Food and Drug Administration (FDA), a biomarker is "a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic intervention" (FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Glossary. 2016 [Updated 2021 Nov 29, cited 2024 Apr 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK338448/ Co-published by National Institutes of Health (US), Bethesda (MD)). The European Medicines Agency (EMA) defines a biomarker as "an objective and quantifiable measure of a physiological process, pathological process or response to a treatment (excluding measurements of how an individual feels or functions" European Medicines Agency (EMA). Biomaker. 2020a. Available from: https://www.ema.europa.eu/en/glossary-terms/biomarker#:~:text=Biomarker-,Biomarker,an%20individual%20feels%20or%20functions . Several clinical biomarkers are well-documented and have been used routinely for decades in health care settings and have long been accepted as valid endpoints for drug approval (for example, blood pressure measurement as a biomarker for cardiovascular health) (European Medicines Agency (EMA). Assessment report, TAGRISSO. 2016. Available from: https://www.ema.europa.eu/en/documents/assessment-report/tagrisso-epar-public-assessment-report_en.pdf . Accessed 15 Apr 2024). Recently, novel biomarkers have been identified and validated to accelerate developing innovative therapies indicated for serious human diseases, for example targeted/immune therapies of cancer (Chen in Med Drug Discov 21:100174, 2024). As indicators of the efficacy of new pharmacological treatments or therapeutic interventions, biomarkers can improve clinical trial efficacy and reduce uncertainty in regulatory decision making (Bakker et al. in Clin Pharmacol Ther 112:69-80, 2022; Califf in Exp Biol Med 243:213-221, 2018; Parker et al. in Cancer Med 10:1955-1963, 2021).

METHODOLOGY: This article describes case studies of recent drug approvals that successfully leveraged validated and non-validated biomarkers (i.e., tofersen for the neurodegenerative disease amyotrophic lateral sclerosis (ALS) in adults; and osimertinib for treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC)).

CONCLUSIONS: Best practices for biomarker selection and strategies for health authority biomarker qualification programs are presented along with an overview of current limitations and challenges to optimizing biomarker applications along the drug development continuum from regulatory, translational, and operational perspectives.},
}

*Drug Development/legislation & jurisprudence
Humans
*Biomarkers
United States
United States Food and Drug Administration
Drug Approval