@article {pmid38708921,
year = {2024},
author = {Monteiro, KLC and Dos Santos Alcântara, MG and de Aquino, TM and da Silva-Júnior, EF},
title = {Insights on Natural Products Against Amyotrophic Lateral Sclerosis (ALS).},
journal = {Current neuropharmacology},
volume = {22},
number = {7},
pages = {1169-1188},
pmid = {38708921},
issn = {1875-6190},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Biological Products/therapeutic use/pharmacology ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Plants, Medicinal/chemistry ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes the death of motor neurons and consequent muscle paralysis. Despite many efforts to address it, current therapy targeting ALS remains limited, increasing the interest in complementary therapies. Over the years, several herbal preparations and medicinal plants have been studied to prevent and treat this disease, which has received remarkable attention due to their blood-brain barrier penetration properties and low toxicity. Thus, this review presents the therapeutic potential of a variety of medicinal herbs and their relationship with ALS and their physiopathological pathways.},
}

*Amyotrophic Lateral Sclerosis/drug therapy
Humans
*Biological Products/therapeutic use/pharmacology
Animals
Neuroprotective Agents/therapeutic use/pharmacology
Plants, Medicinal/chemistry

@article {pmid38705104,
year = {2024},
author = {Dharmadasa, T and Pavey, N and Tu, S and Menon, P and Huynh, W and Mahoney, CJ and Timmins, HC and Higashihara, M and van den Bos, M and Shibuya, K and Kuwabara, S and Grosskreutz, J and Kiernan, MC and Vucic, S},
title = {Novel approaches to assessing upper motor neuron dysfunction in motor neuron disease/amyotrophic lateral sclerosis: IFCN handbook chapter.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {163},
number = {},
pages = {68-89},
doi = {10.1016/j.clinph.2024.04.010},
pmid = {38705104},
issn = {1872-8952},
abstract = {Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function. Single, paired- and triple pulse TMS techniques have yielded novel diagnostic and prognostic biomarkers in MND, and have provided important pathogenic insights, particularly pertaining to site of disease onset. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation, has been associated with the onset of lower motor neuron degeneration, along with patterns of disease spread, development of specific clinical features such as the split hand phenomenon, and may provide an indication about the rate of disease progression. Additionally, reduction of SICI has emerged as a potential diagnostic aid in MND. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction in MND. Separately, sophisticated brain imaging techniques have uncovered novel biomarkers of neurodegeneration that have bene associated with progression. The present review will discuss the utility of TMS and brain neuroimaging derived biomarkers of UMN dysfunction in MND, focusing on recently developed TMS techniques and advanced neuroimaging modalities that interrogate structural and functional integrity of the corticomotoneuronal system, with an emphasis on pathogenic, diagnostic, and prognostic utility.},
}

@article {pmid38702287,
year = {2024},
author = {Tazir, M and Nouioua, S},
title = {Distal hereditary motor neuropathies.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2023.09.005},
pmid = {38702287},
issn = {0035-3787},
abstract = {Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous hereditary disorders characterized by a slowly progressive distal pure motor neuropathy. Electrophysiology, with normal motor and sensory conduction velocities, can suggest the diagnosis of dHMN and guide the genetic study. More than thirty genes are currently associated with HMNs, but around 60 to 70% of cases of dHMN remain uncharacterized genetically. Recent cohort studies showed that HSPB1, GARS, BICB2 and DNAJB2 are among the most frequent dHMN genes and that the prevalence of the disease was calculated as 2.14 and 2.3 per 100,000. The determination of the different genes involved in dHMNs made it possible to observe a genotypic overlap with some other neurogenetic disorders and other hereditary neuropathies such as CMT2, mainly with the HSPB1, HSPB8, BICD2 and TRPV4 genes of AD-inherited transmission and recently observed with SORD gene of AR transmission which seems relatively frequent and potentially curable. Distal hereditary motor neuropathy that predominates in the upper limbs is linked mainly to three genes: GARS, BSCL2 and REEP1, whereas dHMN with vocal cord palsy is associated with SLC5A7, DCTN1 and TRPV4 genes. Among the rare AR forms of dHMN like IGHMBP2 and DNAJB2, the SIGMAR1 gene mutations as well as VRK1 variants are associated with a motor neuropathy phenotype often associated with upper motoneuron involvement. The differential diagnosis of these latter arises with juvenile forms of amyotrophic lateral sclerosis, that could be caused also by variations of these genes, as well as hereditary spastic paraplegia. A differential diagnosis of dHMN related to Brown Vialetto Van Laere syndrome due to riboflavin transporter deficiency is important to consider because of the therapeutic possibility.},
}

@article {pmid38700207,
year = {2024},
author = {Keeley, O and Coyne, AN},
title = {Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease.},
journal = {Nucleus (Austin, Tex.)},
volume = {15},
number = {1},
pages = {2349085},
doi = {10.1080/19491034.2024.2349085},
pmid = {38700207},
issn = {1949-1042},
mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Animals ; Cell Nucleus/metabolism ; Frontotemporal Dementia/metabolism/pathology/genetics ; Endosomes/metabolism ; },
abstract = {The ESCRT machinery plays a pivotal role in membrane-remodeling events across multiple cellular processes including nuclear envelope repair and reformation, nuclear pore complex surveillance, endolysosomal trafficking, and neuronal pruning. Alterations in ESCRT-III functionality have been associated with neurodegenerative diseases including Frontotemporal Dementia (FTD), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease (AD). In addition, mutations in specific ESCRT-III proteins have been identified in FTD/ALS. Thus, understanding how disruptions in the fundamental functions of this pathway and its individual protein components in the human central nervous system (CNS) may offer valuable insights into mechanisms underlying neurodegenerative disease pathogenesis and identification of potential therapeutic targets. In this review, we discuss ESCRT components, dynamics, and functions, with a focus on the ESCRT-III pathway. In addition, we explore the implications of altered ESCRT-III function for neurodegeneration with a primary emphasis on nuclear surveillance and endolysosomal trafficking within the CNS.},
}

Humans
*Endosomal Sorting Complexes Required for Transport/metabolism
*Neurodegenerative Diseases/metabolism/pathology/genetics
Animals
Cell Nucleus/metabolism
Frontotemporal Dementia/metabolism/pathology/genetics
Endosomes/metabolism

@article {pmid38408864,
year = {2024},
author = {Odierna, GL and Vucic, S and Dyer, M and Dickson, T and Woodhouse, A and Blizzard, C},
title = {How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?.},
journal = {Brain : a journal of neurology},
volume = {147},
number = {5},
pages = {1610-1621},
doi = {10.1093/brain/awae039},
pmid = {38408864},
issn = {1460-2156},
support = {//Motor Neuron Disease Research Australia/ ; //National Health and Medical Research Council of Australia/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Motor Neurons/physiology ; *Glutamic Acid/metabolism ; Animals ; Motor Cortex/physiopathology ; },
abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the 'dying forward' excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor neurons spreads pathology to lower motor neurons in the spinal cord in the form of excessive glutamate release, which triggers excitotoxic processes. Many clinical trials have focused on therapies that target excitotoxicity via dampening neuronal activation, but not all are effective. As such, there is a growing tension between the rising tide of evidence for the 'dying forward' excitotoxicity hypothesis and the failure of therapies that target neuronal activation. One possible solution to these contradictory outcomes is that our interpretation of the current evidence requires revision in the context of appreciating the complexity of the nervous system and the limitations of the neurobiological assays we use to study it. In this review we provide an evaluation of evidence relevant to the 'dying forward' excitotoxicity hypothesis and by doing so, identify key gaps in our knowledge that need to be addressed. We hope to provide a road map from hyperexcitability to excitotoxicity so that we can better develop therapies for patients suffering from amyotrophic lateral sclerosis. We conclude that studies of upper motor neuron activity and their synaptic output will play a decisive role in the future of amyotrophic lateral sclerosis therapy.},
}

*Amyotrophic Lateral Sclerosis/physiopathology
Humans
*Motor Neurons/physiology
*Glutamic Acid/metabolism
Animals
Motor Cortex/physiopathology

@article {pmid38694387,
year = {2024},
author = {Arora, H and Javed, B and Kutikuppala, LVS and Chaurasia, M and Khullar, K and Kannan, S and Golla, V},
title = {ST2 levels and neurodegenerative diseases: is this a significant relation?.},
journal = {Annals of medicine and surgery (2012)},
volume = {86},
number = {5},
pages = {2812-2817},
doi = {10.1097/MS9.0000000000001939},
pmid = {38694387},
issn = {2049-0801},
abstract = {Interleukin-33 (IL-33), belonging to the interleukin-1 cytokine family, has a decoy receptor soluble ST2 (sST2). IL-33 is found in oligodendrocytes and astrocytes and is involved in central nervous system healing and repair, whereas ST2 is found in microglia and astrocytes. Some studies have found a link between changes in the IL-33/ST2 pathway and neurodegenerative disorders. This review article investigates the relationship between the interleukin-33 (IL-33)/ST2 pathway and neurodegenerative disorders. It was discovered that soluble st2 levels were increased. Furthermore, IL-33 levels were found to be lower in many neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS). The association with other disorders, such as ankylosing spondylitis, multiple sclerosis, and systemic lupus erythematosus (SLE), was also observed. Various studies suggest that ST2/IL-33 signalling may be pivotal in the disease modulation of neurodegenerative disorders. The serum sST2 level test can be useful in determining the inflammatory status and severity of illness in many neurodegenerative disorders. In this review, we will discuss recent findings concerning the interleukin-33 (IL-33)/ST2 pathway and its role in the diagnosis and treatment of diseases with neurodegeneration.},
}

@article {pmid38459794,
year = {2024},
author = {Campagne, S},
title = {U1 snRNP Biogenesis Defects in Neurodegenerative Diseases.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {25},
number = {9},
pages = {e202300864},
doi = {10.1002/cbic.202300864},
pmid = {38459794},
issn = {1439-7633},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Ribonucleoprotein, U1 Small Nuclear/metabolism/chemistry ; Animals ; },
abstract = {The U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection between disrupted U snRNP biogenesis and several prominent human diseases, notably various neurodegenerative conditions. The perturbation of U1 snRNP homeostasis has been firmly established in diseases such as Spinal Muscular Atrophy, Pontocerebellar hypoplasia, and FUS-mediated Amyotrophic Lateral Sclerosis. Intriguingly, compelling evidence suggests a potential correlation in Fronto-temporal dementia and Alzheimer's disease as well. Although the U snRNP biogenesis pathway is conserved across all eukaryotic cells, neurons, in particular, appear to be highly susceptible to alterations in spliceosome homeostasis. In contrast, other cell types exhibit a greater resilience to such disturbances. This vulnerability underscores the intricate relationship between U1 snRNP dynamics and the health of neuronal cells, shedding light on potential avenues for understanding and addressing neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology
*Ribonucleoprotein, U1 Small Nuclear/metabolism/chemistry
Animals

@article {pmid38691665,
year = {2024},
author = {Singh, P and Belliveau, P and Towle, J and Neculau, AE and Dima, L},
title = {Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.},
journal = {American journal of therapeutics},
volume = {31},
number = {3},
pages = {e258-e267},
doi = {10.1097/MJT.0000000000001742},
pmid = {38691665},
issn = {1536-3686},
mesh = {*Edaravone/administration & dosage/pharmacology/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neuroprotective Agents/administration & dosage/therapeutic use/adverse effects ; Administration, Oral ; Suspensions ; Biological Availability ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone.

MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals.

PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates.

CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure.

THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.},
}

*Edaravone/administration & dosage/pharmacology/therapeutic use
Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Neuroprotective Agents/administration & dosage/therapeutic use/adverse effects
Administration, Oral
Suspensions
Biological Availability

@article {pmid38676818,
year = {2024},
author = {Kubat, GB and Picone, P},
title = {Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {38676818},
issn = {1590-3478},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.},
}

@article {pmid38676672,
year = {2024},
author = {Kutlubaev, MA},
title = {[Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {124},
number = {4},
pages = {13-21},
doi = {10.17116/jnevro202412404113},
pmid = {38676672},
issn = {1997-7298},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Neuroprotective Agents/therapeutic use ; Genetic Therapy ; Antioxidants/therapeutic use ; Stem Cell Transplantation ; Gastrointestinal Microbiome ; Immunologic Factors/therapeutic use ; Immunomodulating Agents/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis is a severe incurable disease of the nervous system. Currently only methods of palliative care for the patients with this disease are available. Few medications for the pathogenetic therapy are registered in some countries, i.e. riluzole, edaravon, sodium phenylbutyrate/taurursodiol as well as tofersen (conditionally). Their efficacy is relatively low. The main directions in the development of pathogenetic therapy of ALS include gene therapy, use of stem cells, immunomodulators, agents affecting gut microbiota. A search is also underway for low-molecular compounds with neuroprotective and antioxidant properties. Perspective direction is prevention of ALS. This will be possible when biomarkers for identification of patients in pre-manifest/prodromal stage are detected.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/therapy
Humans
*Neuroprotective Agents/therapeutic use
Genetic Therapy
Antioxidants/therapeutic use
Stem Cell Transplantation
Gastrointestinal Microbiome
Immunologic Factors/therapeutic use
Immunomodulating Agents/therapeutic use

@article {pmid38674921,
year = {2024},
author = {Wang, W and Pan, D and Liu, Q and Chen, X and Wang, S},
title = {L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.},
journal = {Nutrients},
volume = {16},
number = {8},
pages = {},
pmid = {38674921},
issn = {2072-6643},
mesh = {Humans ; *Carnitine/therapeutic use ; *Nervous System Diseases/drug therapy ; *Mental Disorders/drug therapy ; Dietary Supplements ; },
abstract = {OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.

METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search.

RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation.

CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.},
}

Humans
*Carnitine/therapeutic use
*Nervous System Diseases/drug therapy
*Mental Disorders/drug therapy
Dietary Supplements

@article {pmid38674431,
year = {2024},
author = {Shahim, P and Norato, G and Sinaii, N and Zetterberg, H and Blennow, K and Chan, L and Grunseich, C},
title = {Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Genes},
volume = {15},
number = {4},
pages = {},
pmid = {38674431},
issn = {2073-4425},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis/cerebrospinal fluid ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Biomarkers/blood/cerebrospinal fluid ; Intermediate Filaments/metabolism/genetics ; Prognosis ; },
abstract = {BACKGROUND: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.

METHODS: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.

RESULTS: Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.

DISCUSSION: Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.},
}

*Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis/cerebrospinal fluid
Humans
*Neurofilament Proteins/blood/cerebrospinal fluid
Biomarkers/blood/cerebrospinal fluid
Intermediate Filaments/metabolism/genetics
Prognosis

@article {pmid38672416,
year = {2024},
author = {Cheslow, L and Snook, AE and Waldman, SA},
title = {Biomarkers for Managing Neurodegenerative Diseases.},
journal = {Biomolecules},
volume = {14},
number = {4},
pages = {},
pmid = {38672416},
issn = {2218-273X},
support = {1R01 CA204881, 1R01 CA206026, 1R21 1NS130388, 1R01 DK1388341/NH/NIH HHS/United States ; },
mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/metabolism/diagnosis/therapy ; *Alzheimer Disease/metabolism/diagnosis/therapy ; Amyotrophic Lateral Sclerosis/metabolism/therapy/diagnosis ; Parkinson Disease/metabolism/diagnosis/therapy ; Animals ; },
abstract = {Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).},
}

Humans
*Biomarkers/metabolism
*Neurodegenerative Diseases/metabolism/diagnosis/therapy
*Alzheimer Disease/metabolism/diagnosis/therapy
Amyotrophic Lateral Sclerosis/metabolism/therapy/diagnosis
Parkinson Disease/metabolism/diagnosis/therapy
Animals

@article {pmid38670433,
year = {2024},
author = {Sitruk-Ware, R and Sussman, H and Brinton, R and Schumacher, M and Singer, P and Kumar, N and De Nicola, AF and El-Etr, M and Guennoun, R and V Borlongan, C},
title = {Nestorone (segesterone acetate) effects on neuroregeneration.},
journal = {Frontiers in neuroendocrinology},
volume = {},
number = {},
pages = {101136},
doi = {10.1016/j.yfrne.2024.101136},
pmid = {38670433},
issn = {1095-6808},
abstract = {Nestorone® (segesterone acetate) is a progestin with a chemical structure closely related to progesterone with high affinity and selectivity for the progesterone receptor without significant interaction with other steroid receptors. It has been developed for female and male contraception and is FDA-approved in a first long-acting contraceptive vaginal system for female contraception. Its safety has been extensively demonstrated in both preclinical and clinical studies for contraceptive indications. Nestorone was found to display neuroprotective and neuroregenerative activity in animal models of various central nervous system diseases, including multiple sclerosis, stroke, and amyotrophic lateral sclerosis. Reviewed herein are neuroprotective and myelin- regenerating properties of Nestorone in various animal models and its translational potential as a therapeutic agent for debilitating neurological diseases for which limited therapeutic options are available (Table 1).},
}

@article {pmid38667285,
year = {2024},
author = {Alzahrani, FA and Riza, YM and Eid, TM and Almotairi, R and Scherschinski, L and Contreras, J and Nadeem, M and Perez, SE and Raikwar, SP and Jha, RM and Preul, MC and Ducruet, AF and Lawton, MT and Bhatia, K and Akhter, N and Ahmad, S},
title = {Exosomes in Vascular/Neurological Disorders and the Road Ahead.},
journal = {Cells},
volume = {13},
number = {8},
pages = {},
pmid = {38667285},
issn = {2073-4409},
mesh = {*Exosomes/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/pathology ; Vascular Diseases/metabolism/pathology ; Nervous System Diseases/metabolism/pathology ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.},
}

*Exosomes/metabolism
Humans
Animals
Neurodegenerative Diseases/metabolism/pathology
Vascular Diseases/metabolism/pathology
Nervous System Diseases/metabolism/pathology

@article {pmid38664109,
year = {2024},
author = {Hastings, RL and Valdez, G},
title = {Origin, identity, and function of terminal Schwann cells.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2024.03.007},
pmid = {38664109},
issn = {1878-108X},
abstract = {The highly specialized nonmyelinating glial cells present at somatic peripheral nerve endings, known collectively as terminal Schwann cells (TSCs), play critical roles in the development, function and repair of their motor and sensory axon terminals and innervating tissue. Over the past decades, research efforts across various vertebrate species have revealed that while TSCs are a diverse group of cells, they share a number of features among them. In this review, we summarize the state-of-knowledge about each TSC type and explore the opportunities that TSCs provide to treat conditions that afflict peripheral axon terminals.},
}

@article {pmid38644578,
year = {2024},
author = {Yao, Q and Long, C and Yi, P and Zhang, G and Wan, W and Rao, X and Ying, J and Liang, W and Hua, F},
title = {C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.},
journal = {CNS neuroscience & therapeutics},
volume = {30},
number = {4},
pages = {e14721},
pmid = {38644578},
issn = {1755-5949},
support = {jxsq2019201023//Jiangxi Province "Double Thousand Plan"/ ; 82060219//National Natural Science Foundation of China/ ; 82271234//National Natural Science Foundation of China/ ; 20212ACB216009//Natural Science Foundation of Jiangxi Province/ ; 20212BAB216048//Natural Science Foundation of Jiangxi Province/ ; 2019YNTD12003//Youth Team Project of the Second Affiliated Hospital of Nanchang University/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; *Disease Progression ; Animals ; Amyloid beta-Peptides/metabolism ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.

AIMS: Several studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.

METHODS: A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.

RESULTS: Overexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).

DISCUSSION: The correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).

CONCLUSION: The overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics
*Disease Progression
Animals
Amyloid beta-Peptides/metabolism

@article {pmid38631798,
year = {2024},
author = {Gerecht, RB and Nable, JV},
title = {Out-of-Hospital Cardiac Arrest.},
journal = {Cardiology clinics},
volume = {42},
number = {2},
pages = {317-331},
doi = {10.1016/j.ccl.2024.02.014},
pmid = {38631798},
issn = {1558-2264},
mesh = {Humans ; *Out-of-Hospital Cardiac Arrest ; *Cardiopulmonary Resuscitation ; *Emergency Medical Services ; },
abstract = {Survival from out-of-hospital cardiac arrest (OHCA) is predicated on a community and system-wide approach that includes rapid recognition of cardiac arrest, capable bystander CPR, effective basic and advanced life support (BLS and ALS) by EMS providers, and coordinated postresuscitation care. Management of these critically ill patients continues to evolve. This article focuses on the management of OHCA by EMS providers.},
}

Humans
*Out-of-Hospital Cardiac Arrest
*Cardiopulmonary Resuscitation
*Emergency Medical Services

@article {pmid38630299,
year = {2024},
author = {Wolff, A and Demleitner, AF and Feneberg, E and Lingor, P},
title = {[Smell the smoke before one sees the fire-The oligosymptomatic prodromal phase of neurodegenerative diseases].},
journal = {Der Nervenarzt},
volume = {},
number = {},
pages = {},
pmid = {38630299},
issn = {1433-0407},
abstract = {BACKGROUND: With the increasing development of disease-modifying causative treatment, the importance of early diagnosis and detection of asymptomatic or oligosymptomatic early stages of neurodegenerative diseases is increasing.

OBJECTIVE: Presentation of early stages of neurodegenerative diseases, diagnostic procedures for the early detection and possible treatment consequences.

MATERIAL AND METHODS: Selective literature search, discussion of basic research and expert recommendations.

RESULTS: Many neurodegenerative diseases have a prodromal phase preceding the manifest disease that can be diagnosed with current criteria. In this prodromal phase, those affected are often oligosymptomatic but in some cases can already be identified using biomarkers. These developments are already taken into account in diagnostic criteria for some of these prodromal phases. The prodromal phase, in turn, is preceded by an asymptomatic phase which, however, already shows molecular changes and can be identified by biomarkers in some diseases. The early identification and stratification of patients is particularly important when planning studies for disease-modifying treatment, and biomarkers are already being used in clinical trials for this purpose.

DISCUSSION: Biomarker-based identification of individuals in the prodromal phase of neurodegenerative diseases is already possible for some entities. People who show the first signs of a neurodegenerative disease can be referred to centers for clinical trials and observational studies.},
}

@article {pmid38628839,
year = {2023},
author = {Uzunoglu-Ozyurek, E and Önal, G and Dökmeci, S},
title = {Investigating the Therapeutics Effects of Oral Cavity Derived Stem Cells on Neurodegenerative Diseases: A Systematic Review.},
journal = {Basic and clinical neuroscience},
volume = {14},
number = {5},
pages = {565-584},
pmid = {38628839},
issn = {2008-126X},
abstract = {INTRODUCTION: Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells (OCDSCs) on the recovery or therapy of neurodegenerative diseases (NDs), such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington (HD) diseases, and Parkinson disease (PD).

METHODS: An electronic search was accomplished. References of included articles were also manually searched. Studies were critically evaluated for suitability against the inclusion/exclusion criteria and the data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted.

RESULTS: A total of 14 in vivo and 10 in vitro studies met the inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting the positive effect of OCDSCs on PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; meanwhile, moderate evidence was found for the impact of OCDSCs on AD recovery. Limited evidence was found for in vivo studies evaluating HD and ALS.

CONCLUSION: Although studies reported favorable data regarding the OCDSCs on NDs, they presented a considerable risk of bias. Because of heterogeneous study characteristics, the current study recommends improving standardized methods to evaluate the therapeutic effects of OCDSCs on the NDs.},
}

@article {pmid38623278,
year = {2024},
author = {Inci, OK and Basırlı, H and Can, M and Yanbul, S and Seyrantepe, V},
title = {Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.},
journal = {Journal of lipids},
volume = {2024},
number = {},
pages = {4530255},
pmid = {38623278},
issn = {2090-3030},
abstract = {Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.},
}

@article {pmid38621750,
year = {2024},
author = {Kosmachevskaya, OV and Novikova, NN and Yakunin, SN and Topunov, AF},
title = {Formation of Supplementary Metal-Binding Centers in Proteins under Stress Conditions.},
journal = {Biochemistry. Biokhimiia},
volume = {89},
number = {Suppl 1},
pages = {S180-S204},
doi = {10.1134/S0006297924140104},
pmid = {38621750},
issn = {1608-3040},
mesh = {*Metals/chemistry/metabolism ; *Oxidative Stress ; Oxidation-Reduction ; Protein Processing, Post-Translational ; },
abstract = {In many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as "cross-linking" agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special attention is paid to the role of cysteine SH-groups in the formation of supplementary metal-binding centers, since these groups are the main target for the action of reactive species. Supplementary metal binding centers may also appear due to unmasking of amino acid residues when protein conformation changing. Appearance of such centers is usually considered as a pathological process. Such unilateral approach does not allow to obtain an integral view of the phenomenon, ignoring cases when formation of metal complexes with altered proteins is a way to adjust protein properties, activity, and stability under the changed redox conditions. The role of metals in protein aggregation is being studied actively, since it leads to formation of non-membranous organelles, liquid condensates, and solid conglomerates. Some proteins found in such aggregates are typical for various diseases, such as Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and some types of cancer.},
}

*Metals/chemistry/metabolism
*Oxidative Stress
Oxidation-Reduction
Protein Processing, Post-Translational

@article {pmid38621743,
year = {2024},
author = {Rezvykh, A and Shteinberg, D and Bronovitsky, E and Ustyugov, A and Funikov, S},
title = {Animal Models of FUS-Proteinopathy: A Systematic Review.},
journal = {Biochemistry. Biokhimiia},
volume = {89},
number = {Suppl 1},
pages = {S34-S56},
doi = {10.1134/S0006297924140037},
pmid = {38621743},
issn = {1608-3040},
mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; RNA-Binding Protein FUS/genetics/metabolism ; Motor Neurons/metabolism/pathology ; Cytoplasm/metabolism ; Mutation ; Disease Models, Animal ; },
abstract = {Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.},
}

Animals
Humans
*Amyotrophic Lateral Sclerosis/genetics
RNA-Binding Protein FUS/genetics/metabolism
Motor Neurons/metabolism/pathology
Cytoplasm/metabolism
Mutation
Disease Models, Animal

@article {pmid38614367,
year = {2024},
author = {Roghani, AK and Garcia, RI and Roghani, A and Reddy, A and Khemka, S and Reddy, RP and Pattoor, V and Jacob, M and Reddy, PH and Sehar, U},
title = {Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.},
journal = {Ageing research reviews},
volume = {97},
number = {},
pages = {102291},
doi = {10.1016/j.arr.2024.102291},
pmid = {38614367},
issn = {1872-9649},
abstract = {The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.},
}

@article {pmid38612804,
year = {2024},
author = {Giri, PM and Banerjee, A and Ghosal, A and Layek, B},
title = {Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications.},
journal = {International journal of molecular sciences},
volume = {25},
number = {7},
pages = {},
pmid = {38612804},
issn = {1422-0067},
support = {P20 GM109024/GM/NIGMS NIH HHS/United States ; 2P20M109024/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; Neuroinflammatory Diseases ; Inflammation/therapy ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Central Nervous System ; },
abstract = {Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of the total population of the world is affected by some form of NDs, resulting in physical and cognitive disability. The most common NDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although NDs are caused by a complex interaction of genetic, environmental, and lifestyle variables, neuroinflammation is known to be associated with all NDs, often leading to permanent damage to neurons of the central nervous system. Furthermore, numerous emerging pieces of evidence have demonstrated that inflammation not only supports the progression of NDs but can also serve as an initiator. Hence, various medicines capable of preventing or reducing neuroinflammation have been investigated as ND treatments. While anti-inflammatory medicine has shown promising benefits in several preclinical models, clinical outcomes are often questionable. In this review, we discuss various NDs with their current treatment strategies, the role of neuroinflammation in the pathophysiology of NDs, and the use of anti-inflammatory agents as a potential therapeutic option.},
}

Humans
Neuroinflammatory Diseases
Inflammation/therapy
*Alzheimer Disease
*Amyotrophic Lateral Sclerosis
Central Nervous System

@article {pmid38612448,
year = {2024},
author = {Homma, H and Tanaka, H and Fujita, K and Okazawa, H},
title = {Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease.},
journal = {International journal of molecular sciences},
volume = {25},
number = {7},
pages = {},
pmid = {38612448},
issn = {1422-0067},
mesh = {Humans ; *HMGB1 Protein ; *Neurodegenerative Diseases ; Neuroinflammatory Diseases ; Necrosis ; Cell Death ; },
abstract = {The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death. The present review provides an updated summary of necrosis subtypes and discusses their potential roles in neurodegenerative cell death. Among numerous necrosis subtypes, including necroptosis, paraptosis, ferroptosis, and pyroptosis, transcriptional repression-induced atypical cell death (TRIAD) has been identified as a potential mechanism of neuronal cell death. TRIAD is induced by functional deficiency of TEAD-YAP and self-amplifies via the release of HMGB1. TRIAD is a feasible potential mechanism of neuronal cell death in Alzheimer's disease and other neurodegenerative diseases. In addition to induction of cell death, HMGB1 released during TRIAD activates brain inflammatory responses, which is a potential link between neurodegeneration and neuroinflammation.},
}

Humans
*HMGB1 Protein
*Neurodegenerative Diseases
Neuroinflammatory Diseases
Necrosis
Cell Death

@article {pmid38610192,
year = {2024},
author = {Papadopoulou, M and Papapostolou, A and Dimakopoulos, R and Salakou, S and Koropouli, E and Fanouraki, S and Bakola, E and Moschovos, C and Tsivgoulis, G},
title = {Non-Pharmacological Interventions on Pain in Amyotrophic Lateral Sclerosis Patients: A Systematic Review and Meta-Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {12},
number = {7},
pages = {},
pmid = {38610192},
issn = {2227-9032},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs; thus, ALS is considered a multisystemic disorder. Pain is an important nonmotor symptom. Observational and case-control studies report high frequency of pain in ALS patients and it has been correlated with depression and quality of life. There are no specific scales for the assessment of pain and no randomized controlled trials (RCTs) regarding the drug management of pain in ALS.

AIM: To systematically review the evidence for the nonpharmacological interventions (NPIs) in relieving pain in ALS, on March 2024, we searched the following databases: Pubmed, Scopus, Web of Science, and Cochrane. We also checked the bibliographies of trials identified to include further published or unpublished trials.

MAIN RESULTS: A total of 1003 records were identified. Finally, five RCTs including 131 patients (64 in the intervention group and 67 in the control group) were included for meta-analysis. The interventions of the included RCTs consisted of muscle exercise, combined aerobics-strength intervention, and osteopathic manual treatment. The meta-analysis did not find a statistically significant difference in favor of NPIs for alleviating pain in ALS patients.

CONCLUSIONS: ALS has a fulminant course and irreversibly leads to death. Pain in ALS patients, although a common nonmotor symptom, is often unrecognized and undertreated, and this is underlined by the lack of any RCTs on drug therapy for pain. Albeit NPIs are considered safe, as adverse effects are rarely reported, this systematic review did not provide sufficient evidence for a beneficial effect on pain. The scarceness of relevant literature highlights the need for future studies, with larger samples, more homogeneous in terms of interventions and population characteristics (stage of disease), and better choice of measurement scales to further investigate the efficacy, if any, of various pain interventions in ALS patients.},
}

@article {pmid38610012,
year = {2024},
author = {Liu, X and Shen, L and Wan, M and Xie, H and Wang, Z},
title = {Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles.},
journal = {Journal of nanobiotechnology},
volume = {22},
number = {1},
pages = {170},
pmid = {38610012},
issn = {1477-3155},
support = {82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 2020YFC2008500//National Key R&D Program of China/ ; },
mesh = {Humans ; Prospective Studies ; *Extracellular Vesicles ; *Exosomes ; *Parkinson Disease ; *Alzheimer Disease ; },
abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies. Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: "neurodegenerative disease" OR "Alzheimer's disease" OR "Parkinson's disease" OR "Amyotrophic lateral sclerosis" AND "extracellular vesicles" OR "exosomes" OR "outer membrane vesicles" AND "drug delivery systems" AND "blood-brain barrier". MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.},
}

Humans
Prospective Studies
*Extracellular Vesicles
*Exosomes
*Parkinson Disease
*Alzheimer Disease

@article {pmid38609750,
year = {2024},
author = {Sellier, C and Corcia, P and Vourc'h, P and Dupuis, L},
title = {C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2024.03.008},
pmid = {38609750},
issn = {0035-3787},
abstract = {The major gene underlying monogenic forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is C9ORF72. The causative mutation in C9ORF72 is an abnormal hexanucleotide (G4C2) repeat expansion (HRE) located in the first intron of the gene. The aim of this review is to propose a comprehensive update on recent developments on clinical, biological and therapeutics aspects related to C9ORF72 in order to highlight the current understanding of genotype-phenotype correlations, and also on biological machinery leading to neuronal death. We will particularly focus on the broad phenotypic presentation of C9ORF72-related diseases, that goes well beyond the classical phenotypes observed in ALS and FTD patients. Last, we will comment the possible therapeutical hopes for patients carrying a C9ORF72 HRE.},
}

@article {pmid38609644,
year = {2024},
author = {Khalil, M and Teunissen, CE and Lehmann, S and Otto, M and Piehl, F and Ziemssen, T and Bittner, S and Sormani, MP and Gattringer, T and Abu-Rumeileh, S and Thebault, S and Abdelhak, A and Green, A and Benkert, P and Kappos, L and Comabella, M and Tumani, H and Freedman, MS and Petzold, A and Blennow, K and Zetterberg, H and Leppert, D and Kuhle, J},
title = {Neurofilaments as biomarkers in neurological disorders - towards clinical application.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {38609644},
issn = {1759-4766},
abstract = {Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.},
}

@article {pmid38607083,
year = {2024},
author = {Tamberi, L and Belloni, A and Pugnaloni, A and Rippo, MR and Olivieri, F and Procopio, AD and Bronte, G},
title = {The Influence of Myeloid-Derived Suppressor Cell Expansion in Neuroinflammation and Neurodegenerative Diseases.},
journal = {Cells},
volume = {13},
number = {7},
pages = {},
pmid = {38607083},
issn = {2073-4409},
mesh = {Humans ; *Myeloid-Derived Suppressor Cells/pathology ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/pathology ; Inflammation/pathology ; Cell Proliferation ; },
abstract = {The neuro-immune axis has a crucial function both during physiological and pathological conditions. Among the immune cells, myeloid-derived suppressor cells (MDSCs) exert a pivotal role in regulating the immune response in many pathological conditions, influencing neuroinflammation and neurodegenerative disease progression. In chronic neuroinflammation, MDSCs could lead to exacerbation of the inflammatory state and eventually participate in the impairment of cognitive functions. To have a complete overview of the role of MDSCs in neurodegenerative diseases, research on PubMed for articles using a combination of terms made with Boolean operators was performed. According to the search strategy, 80 papers were retrieved. Among these, 44 papers met the eligibility criteria. The two subtypes of MDSCs, monocytic and polymorphonuclear MDSCs, behave differently in these diseases. The initial MDSC proliferation is fundamental for attenuating inflammation in Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), but not in amyotrophic lateral sclerosis (ALS), where MDSC expansion leads to exacerbation of the disease. Moreover, the accumulation of MDSC subtypes in distinct organs changes during the disease. The proliferation of MDSC subtypes occurs at different disease stages and can influence the progression of each neurodegenerative disorder differently.},
}

Humans
*Myeloid-Derived Suppressor Cells/pathology
Neuroinflammatory Diseases
*Neurodegenerative Diseases/pathology
Inflammation/pathology
Cell Proliferation

@article {pmid38603949,
year = {2024},
author = {Shin-Yi Lin, C and Howells, J and Rutkove, S and Nandedkar, S and Neuwirth, C and Noto, YI and Shahrizaila, N and Whittaker, RG and Bostock, H and Burke, D and Tankisi, H},
title = {Neurophysiological and imaging biomarkers of lower motor neuron dysfunction in motor neuron diseases/amyotrophic lateral sclerosis: IFCN handbook chapter.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {162},
number = {},
pages = {91-120},
doi = {10.1016/j.clinph.2024.03.015},
pmid = {38603949},
issn = {1872-8952},
abstract = {This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.g. MScanFit MUNE) or voluntary activation (MUNIX). Electrical impedance myography (EIM) is another novel approach for the evaluation that relies upon the application and measurement of high-frequency, low-intensity electrical current. Nerve excitability techniques (NET) also provide insights into the function of an axon and reflect the changes in resting membrane potential, ion channel dysfunction and the structural integrity of the axon and myelin sheath. Furthermore, imaging ultrasound techniques as well as magnetic resonance imaging are capable of detecting the constituents of morphological changes in the nerve and muscle. The chapter provides a critical description of the ability of each technique to provide neurophysiological insight into the complex pathophysiology of MND/ALS. However, it is important to recognise the strengths and limitations of each approach in order to clarify utility. These neurophysiological biomarkers have demonstrated reliability, specificity and provide additional information to validate and assess lower motor neuron dysfunction. Their use has expanded the knowledge about MND/ALS and enhanced our understanding of the relationship between motor units, axons, reflexes and other neural circuits in relation to clinical features of patients with MND/ALS at different stages of the disease. Taken together, the ultimate goal is to aid early diagnosis, distinguish potential disease mimics, monitor and stage disease progression, quantify response to treatment and develop potential therapeutic interventions.},
}

@article {pmid38600725,
year = {2024},
author = {Madhubala, D and Patra, A and Khan, MR and Mukherjee, AK},
title = {Phytomedicine for neurodegenerative diseases: The road ahead.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.8192},
pmid = {38600725},
issn = {1099-1573},
support = {//IASST/ ; EMR/2017/001829//Science and Engineering Research Board/ ; },
abstract = {Neurodegenerative disorders (NDs) are among the most common causes of death across the globe. NDs are characterized by progressive damage to CNS neurons, leading to defects in specific brain functions such as memory, cognition, and movement. The most common NDs are Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). Despite extensive research, no therapeutics or medications against NDs have been proven to be effective. The current treatment of NDs involving symptom-based targeting of the disease pathogenesis has certain limitations, such as drug resistance, adverse side effects, poor blood-brain barrier permeability, and poor bioavailability of drugs. Some studies have shown that plant-derived natural compounds hold tremendous promise for treating and preventing NDs. Therefore, the primary objective of this review article is to critically analyze the properties and potency of some of the most studied phytomedicines, such as quercetin, curcumin, epigallocatechin gallate (EGCG), apigenin, and cannabinoids, and highlight their advantages and limitations for developing next-generation alternative treatments against NDs. Further extensive research on pre-clinical and clinical studies for developing plant-based drugs against NDs from bench to bedside is warranted.},
}

@article {pmid38599171,
year = {2024},
author = {Castro-Gomez, S and Heneka, MT},
title = {Innate immune activation in neurodegenerative diseases.},
journal = {Immunity},
volume = {57},
number = {4},
pages = {790-814},
doi = {10.1016/j.immuni.2024.03.010},
pmid = {38599171},
issn = {1097-4180},
mesh = {Humans ; *Neurodegenerative Diseases ; Receptors, Pattern Recognition ; Immune System ; Inflammation Mediators ; Immunity, Innate ; },
abstract = {Activation of the innate immune system following pattern recognition receptor binding has emerged as one of the major pathogenic mechanisms in neurodegenerative disease. Experimental, epidemiological, pathological, and genetic evidence underscores the meaning of innate immune activation during the prodromal as well as clinical phases of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Importantly, innate immune activation and the subsequent release of inflammatory mediators contribute mechanistically to other hallmarks of neurodegenerative diseases such as aberrant proteostatis, pathological protein aggregation, cytoskeleton abnormalities, altered energy homeostasis, RNA and DNA defects, and synaptic and network disbalance and ultimately to the induction of neuronal cell death. In this review, we discuss common mechanisms of innate immune activation in neurodegeneration, with particular emphasis on the pattern recognition receptors (PRRs) and other receptors involved in the detection of damage-associated molecular patterns (DAMPs).},
}

Humans
*Neurodegenerative Diseases
Receptors, Pattern Recognition
Immune System
Inflammation Mediators
Immunity, Innate

@article {pmid38595972,
year = {2024},
author = {Zhou, L and Xie, M and Wang, X and Xu, R},
title = {The usage and advantages of several common amyotrophic lateral sclerosis animal models.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1341109},
pmid = {38595972},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis is a fatal, multigenic, multifactorial neurodegenerative disease characterized by upper and lower motor neuron loss. Animal models are essential for investigating pathogenesis and reflecting clinical manifestations, particularly in developing reasonable prevention and therapeutic methods for human diseases. Over the decades, researchers have established a host of different animal models in order to dissect amyotrophic lateral sclerosis (ALS), such as yeast, worms, flies, zebrafish, mice, rats, pigs, dogs, and more recently, non-human primates. Although these models show different peculiarities, they are all useful and complementary to dissect the pathological mechanisms of motor neuron degeneration in ALS, contributing to the development of new promising therapeutics. In this review, we describe several common animal models in ALS, classified by the naturally occurring and experimentally induced, pointing out their features in modeling, the onset and progression of the pathology, and their specific pathological hallmarks. Moreover, we highlight the pros and cons aimed at helping the researcher select the most appropriate among those common experimental animal models when designing a preclinical ALS study.},
}

@article {pmid38592845,
year = {2024},
author = {Lerose, V and Ponticelli, M and Benedetto, N and Carlucci, V and Lela, L and Tzvetkov, NT and Milella, L},
title = {Withania somnifera (L.) Dunal, a Potential Source of Phytochemicals for Treating Neurodegenerative Diseases: A Systematic Review.},
journal = {Plants (Basel, Switzerland)},
volume = {13},
number = {6},
pages = {},
pmid = {38592845},
issn = {2223-7747},
support = {CUP: B34I20000320005//Project RESO - REsilienza e SOstenibilità delle filiere ortofrutticole e cerealicole per valorizzare i territori" - cod. identif. ARS01_01224 -/ ; CUP: G49J19001350004//Project SPIA-Valorization of by-products from the agro-food chain/ ; CUP: ECS00000036//Project NODES - Ecosistema dell'Innovazione "Nord Ovest Digitale e Sostenibile"/ ; },
abstract = {Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.},
}

@article {pmid38588013,
year = {2024},
author = {El Hajj, R and Al Sagheer, T and Ballout, N},
title = {Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review.},
journal = {Journal of neuroscience research},
volume = {102},
number = {4},
pages = {e25321},
doi = {10.1002/jnr.25321},
pmid = {38588013},
issn = {1097-4547},
mesh = {Animals ; Optogenetics/methods ; *Neurodegenerative Diseases/therapy/drug therapy ; Brain/physiology ; Basal Ganglia ; *Parkinson Disease/genetics ; },
abstract = {Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.},
}

Animals
Optogenetics/methods
*Neurodegenerative Diseases/therapy/drug therapy
Brain/physiology
Basal Ganglia
*Parkinson Disease/genetics

@article {pmid38586597,
year = {2024},
author = {Zhang, T and Bao, L and Chen, H},
title = {Review of Phenotypic Heterogeneity of Neuronal Intranuclear Inclusion Disease and NOTCH2NLC-Related GGC Repeat Expansion Disorders.},
journal = {Neurology. Genetics},
volume = {10},
number = {2},
pages = {e200132},
pmid = {38586597},
issn = {2376-7839},
abstract = {Neuronal intranuclear inclusion disease (NIID) is an underdiagnosed neurodegenerative disorder caused by pathogenic GGC expansions in NOTCH2NLC. However, an increasing number of reports of NOTCH2NLC GGC expansions in patients with Alzheimer disease, essential tremor, Parkinson disease, amyotrophic lateral sclerosis, and oculopharyngodistal myopathy have led to the proposal of a new concept known as NOTCH2NLC-related GGC repeat expansion disorders (NREDs). The majority of studies have mainly focused on screening for NOTCH2NLC GGC repeat variation in populations previously diagnosed with the associated disease, subsequently presenting it as a novel causative gene for the condition. These studies appear to be clinically relevant but do have their limitations because they may incorrectly regard the lack of MRI abnormalities as an exclusion criterion for NIID or overlook concomitant clinical presentations not typically observed in the associated diseases. Besides, in many instances within these reports, patients lack pathologic evidence or undergo long-term follow-up to conclusively rule out NIID. In this review, we will systematically review the research on NOTCH2NLC 5' untranslated region GGC repeat expansions and their association with related neurologic disorders, explaining the limitations of the relevant reports. Furthermore, we will integrate subsequent studies to further demonstrate that these patients actually experienced distinct clinical phenotypes of NIID.},
}

@article {pmid38585631,
year = {2024},
author = {Pinilla-González, V and Montecinos-Barrientos, B and Martin-Kommer, C and Chichiarelli, S and Saso, L and Rodrigo, R},
title = {Exploring antioxidant strategies in the pathogenesis of ALS.},
journal = {Open life sciences},
volume = {19},
number = {1},
pages = {20220842},
pmid = {38585631},
issn = {2391-5412},
abstract = {The central nervous system is essential for maintaining homeostasis and controlling the body's physiological functions. However, its biochemical characteristics make it highly vulnerable to oxidative damage, which is a common factor in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). ALS is a leading cause of motor neuron disease, characterized by a rapidly progressing and incurable condition. ALS often results in death from respiratory failure within 3-5 years from the onset of the first symptoms, underscoring the urgent need to address this medical challenge. The aim of this study is to present available data supporting the role of oxidative stress in the mechanisms underlying ALS and to discuss potential antioxidant therapies currently in development. These therapies aim to improve the quality of life and life expectancy for patients affected by this devastating disease.},
}

@article {pmid38585368,
year = {2024},
author = {Jamet, M and Dupuis, L and Gonzalez De Aguilar, JL},
title = {Oligodendrocytes in amyotrophic lateral sclerosis and frontotemporal dementia: the new players on stage.},
journal = {Frontiers in molecular neuroscience},
volume = {17},
number = {},
pages = {1375330},
pmid = {38585368},
issn = {1662-5099},
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal adult-onset neurodegenerative disorders that share clinical, neuropathological and genetic features, which forms part of a multi-system disease spectrum. The pathological process leading to ALS and FTD is the result of the combination of multiple mechanisms that operate within specific populations of neurons and glial cells. The implication of oligodendrocytes has been the subject of a number of studies conducted on patients and related animal models. In this review we summarize our current knowledge on the alterations specific to myelin and the oligodendrocyte lineage occurring in ALS and FTD. We also consider different ways by which specific oligodendroglial alterations influence neurodegeneration and highlight the important role of oligodendrocytes in these two intrinsically associated neurodegenerative diseases.},
}

@article {pmid38583129,
year = {2024},
author = {Thal, DR and Gawor, K and Moonen, S},
title = {Regulated cell death and its role in Alzheimer's disease and amyotrophic lateral sclerosis.},
journal = {Acta neuropathologica},
volume = {147},
number = {1},
pages = {69},
pmid = {38583129},
issn = {1432-0533},
support = {22-AAIIA-963171/ALZ/Alzheimer's Association/United States ; },
mesh = {Humans ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Regulated Cell Death ; Cell Death ; Motor Neurons ; },
abstract = {Despite considerable research efforts, it is still not clear which mechanisms underlie neuronal cell death in neurodegenerative diseases. During the last 20 years, multiple pathways have been identified that can execute regulated cell death (RCD). Among these RCD pathways, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-related cell death, and lysosome-dependent cell death have been intensively investigated. Although RCD consists of numerous individual pathways, multiple common proteins have been identified that allow shifting from one cell death pathway to another. Another layer of complexity is added by mechanisms such as the endosomal machinery, able to regulate the activation of some RCD pathways, preventing cell death. In addition, restricted axonal degeneration and synaptic pruning can occur as a result of RCD activation without loss of the cell body. RCD plays a complex role in neurodegenerative processes, varying across different disorders. It has been shown that RCD is differentially involved in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), among the most common neurodegenerative diseases. In AD, neuronal loss is associated with the activation of not only necroptosis, but also pyroptosis. In ALS, on the other hand, motor neuron death is not linked to canonical necroptosis, whereas pyroptosis pathway activation is seen in white matter microglia. Despite these differences in the activation of RCD pathways in AD and ALS, the accumulation of protein aggregates immunoreactive for p62/SQSTM1 (sequestosome 1) is a common event in both diseases and many other neurodegenerative disorders. In this review, we describe the major RCD pathways with clear activation in AD and ALS, the main interactions between these pathways, as well as their differential and similar involvement in these disorders. Finally, we will discuss targeting RCD as an innovative therapeutic concept for neurodegenerative diseases, such as AD and ALS. Considering that the execution of RCD or "cellular suicide" represents the final stage in neurodegeneration, it seems crucial to prevent neuronal death in patients by targeting RCD. This would offer valuable time to address upstream events in the pathological cascade by keeping the neurons alive.},
}

Humans
*Alzheimer Disease
*Amyotrophic Lateral Sclerosis
*Regulated Cell Death
Cell Death
Motor Neurons

@article {pmid38575486,
year = {2024},
author = {Chandran, SK and Doucet, M},
title = {Neurogenic Dysphagia.},
journal = {Otolaryngologic clinics of North America},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.otc.2024.02.023},
pmid = {38575486},
issn = {1557-8259},
abstract = {This article provides an overview of neurogenic dysphagia, describing the evaluation and management of swallowing dysfunction in various neurologic diseases. The article will focus on stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis.},
}

@article {pmid38570095,
year = {2024},
author = {Wiblin, L},
title = {An introduction to neuropalliative care: A growing need.},
journal = {Clinical medicine (London, England)},
volume = {24},
number = {2},
pages = {100038},
doi = {10.1016/j.clinme.2024.100038},
pmid = {38570095},
issn = {1473-4893},
abstract = {Palliative care (PC) defined as 'an approach improving the quality of life of patients and their families facing problems associated with life-limiting illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual' aims to enhance the improve the remaining time that patients have, emphasising choice for patients and families.[1] Patients with neurological disease such as Parkinson's (PD) and motor neurone disease (MND) benefit from PC earlier in disease with increasing emphasis over time. Understanding and communicating uncertain trajectories, honest prognostic communication when patients are ready and careful symptom control has been shown to enhance quality of life in patients and caregivers, giving greater autonomy to these patients when supported in decision-making by a palliative approach. Although obstacles to palliative care are frequent, there are strategies which can help overcome them.},
}

@article {pmid38563162,
year = {2024},
author = {Pastora, LE and Namburu, NS and Arora, K and Christov, PP and Wilson, JT},
title = {STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.},
journal = {ACS applied bio materials},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsabm.3c01305},
pmid = {38563162},
issn = {2576-6422},
abstract = {Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.},
}

@article {pmid38563056,
year = {2024},
author = {Umar, TP and Jain, N and Papageorgakopoulou, M and Shaheen, RS and Alsamhori, JF and Muzzamil, M and Kostiks, A},
title = {Artificial intelligence for screening and diagnosis of amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/21678421.2024.2334836},
pmid = {38563056},
issn = {2167-9223},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurological disease that leads to progressive motor function degeneration. Diagnosing ALS is challenging due to the absence of a specific detection test. The use of artificial intelligence (AI) can assist in the investigation and treatment of ALS.

METHODS: We searched seven databases for literature on the application of AI in the early diagnosis and screening of ALS in humans. The findings were summarized using random-effects summary receiver operating characteristic curve. The risk of bias (RoB) analysis was carried out using QUADAS-2 or QUADAS-C tools.

RESULTS: In the 34 analyzed studies, a meta-prevalence of 47% for ALS was noted. For ALS detection, the pooled sensitivity of AI models was 94.3% (95% CI - 63.2% to 99.4%) with a pooled specificity of 98.9% (95% CI - 92.4% to 99.9%). For ALS classification, the pooled sensitivity of AI models was 90.9% (95% CI - 86.5% to 93.9%) with a pooled specificity of 92.3% (95% CI - 84.8% to 96.3%). Based on type of input for classification, the pooled sensitivity of AI models for gait, electromyography, and magnetic resonance signals was 91.2%, 92.6%, and 82.2%, respectively. The pooled specificity for gait, electromyography, and magnetic resonance signals was 94.1%, 96.5%, and 77.3%, respectively.

CONCLUSIONS: Although AI can play a significant role in the screening and diagnosis of ALS due to its high sensitivities and specificities, concerns remain regarding quality of evidence reported in the literature.},
}

@article {pmid38558150,
year = {2024},
author = {Pensato, U and Cortelli, P},
title = {Soccer (football) and brain health.},
journal = {Journal of neurology},
volume = {},
number = {},
pages = {},
pmid = {38558150},
issn = {1432-1459},
abstract = {Soccer is one of the most popular sports worldwide, played by over 270 million people and followed by many more. Several brain health benefits are promoted by practising soccer and physical exercise at large, which helps contrast the cognitive decline associated with ageing by enhancing neurogenesis processes. However, sport-related concussions have been increasingly recognised as a pressing public health concern, not only due to their acute impact but also, more importantly, due to mounting evidence indicating an elevated risk for the development of neurological sequelae following recurrent head traumas, especially chronic traumatic encephalopathy (CTE). While soccer players experience less frequent concussions compared with other contact or combat sports, such as American football or boxing, it stands alone in its purposeful use of the head to hit the ball (headings), setting its players apart as the only athletes exposed to intentional, sub-concussive head impacts. Additionally, an association between soccer and amyotrophic lateral sclerosis has been consistently observed, suggesting a potential "soccer-specific" risk factor. In this review, we discuss the neurological sequelae related to soccer playing, the emerging evidence of a detrimental effect related to recurrent headings, and the need for implementation of comprehensive strategies aimed at preventing and managing the burden of head impact in soccer.},
}

@article {pmid38552851,
year = {2024},
author = {Yang, L and Guttman, L and Dawson, VL and Dawson, TM},
title = {Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {116174},
doi = {10.1016/j.bcp.2024.116174},
pmid = {38552851},
issn = {1873-2968},
support = {R01 AG085688/AG/NIA NIH HHS/United States ; R01 NS067525/NS/NINDS NIH HHS/United States ; },
abstract = {Parthanatos is a cell death signaling pathway that has emerged as a compelling target for pharmaceutical intervention. It plays a pivotal role in the neuron loss and neuroinflammation that occurs in Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), and stroke. There are currently no treatments available to humans to prevent cell death in any of these diseases. This review provides an in-depth examination of the current understanding of the Parthanatos mechanism, with a particular focus on its implications in neuroinflammation and various diseases discussed herein. Furthermore, we thoroughly review potential intervention targets within the Parthanatos pathway. We dissect recent progress in inhibitory strategies, complimented by a detailed structural analysis of key Parthanatos executioners, PARP-1, AIF, and MIF, along with an assessment of their established inhibitors. We hope to introduce a new perspective on the feasibility of targeting components within the Parthanatos pathway, emphasizing its potential to bring about transformative outcomes in therapeutic interventions. By delineating therapeutic opportunities and known targets, we seek to emphasize the imperative of blocking Parthanatos as a precursor to developing disease-modifying treatments. This comprehensive exploration aims to catalyze a paradigm shift in our understanding of potential neurodegenerative disease therapeutics, advocating for the pursuit of effective interventions centered around Parthanatos inhibition.},
}

@article {pmid38550565,
year = {2024},
author = {Di Nardo, AA and Prochiantz, A},
title = {Therapeutic value of homeoprotein signaling pathways.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1359523},
pmid = {38550565},
issn = {1662-4548},
abstract = {Cell signaling based on homeoprotein transfer is a pathway with developmental and physiological functions. For a few transcription factors of this family, primarily ENGRAILED1, ENGRAILED2 and OTX2, their physiological functions have led to therapeutic strategies in animal models of human diseases, including Parkinson's disease, amyotrophic lateral sclerosis, amblyopia and anxiety-related disorders. In mesencephalic dopaminergic neurons which degenerate in Parkinson's disease, ENGRAILED1/2 have cell autonomous activities, but their transducing properties enables their use as therapeutic proteins. In contrast, in spinal alpha-motoneurons, which are lost in amyotrophic lateral sclerosis, ENGRAILED1 is supplied by V1 interneurons. Thus, its use as a therapeutic protein to protect alpha-motoneurons against degeneration mimics its normal non-cell autonomous neurotrophic activity. OTX2, synthesized and secreted by the choroid plexus, is transferred to parvalbumin interneurons and exerts regulatory functions controlling cerebral cortex plasticity. Understanding the latter OTX2 function has led to strategies for manipulating visual acuity and anxiety-like behavior in adult mice. In this review, we describe these cases and what is known about the involved molecular mechanisms. Because the transduction sequences are conserved in most of the few hundred homeoproteins, we argue how this family of molecules constitutes an important reservoir of physiological knowledge, with potential consequences in the search for new therapeutic strategies.},
}

@article {pmid38548126,
year = {2024},
author = {Krut', VG and Kalinichenko, AL and Maltsev, DI and Jappy, D and Shevchenko, EK and Podgorny, OV and Belousov, VV},
title = {Optogenetic and chemogenetic approaches for modeling neurological disorders in vivo.},
journal = {Progress in neurobiology},
volume = {235},
number = {},
pages = {102600},
doi = {10.1016/j.pneurobio.2024.102600},
pmid = {38548126},
issn = {1873-5118},
mesh = {Animals ; Humans ; Optogenetics/methods ; *Epilepsy ; Models, Animal ; *Parkinson Disease ; Neuropathology ; },
abstract = {Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.},
}

Animals
Humans
Optogenetics/methods
*Epilepsy
Models, Animal
*Parkinson Disease
Neuropathology

@article {pmid38542497,
year = {2024},
author = {Nemeth, C and Banik, NL and Haque, A},
title = {Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {6},
pages = {},
pmid = {38542497},
issn = {1422-0067},
support = {1R21NS118393-01/NH/NIH HHS/United States ; },
mesh = {Humans ; Neuromuscular Junction/metabolism ; Motor Neurons/metabolism ; Muscle Fibers, Skeletal/metabolism ; Spinal Cord/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Spinal Cord Injuries/metabolism ; },
abstract = {The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.},
}

Humans
Neuromuscular Junction/metabolism
Motor Neurons/metabolism
Muscle Fibers, Skeletal/metabolism
Spinal Cord/metabolism
*Amyotrophic Lateral Sclerosis/metabolism
*Spinal Cord Injuries/metabolism

@article {pmid38542306,
year = {2024},
author = {Marshall Moscon, SL and Connor, JR},
title = {HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.},
journal = {International journal of molecular sciences},
volume = {25},
number = {6},
pages = {},
pmid = {38542306},
issn = {1422-0067},
mesh = {Mice ; Animals ; *Neurodegenerative Diseases/genetics ; Hemochromatosis Protein/genetics ; Histocompatibility Antigens Class I/genetics ; Hormesis ; Mutation ; Iron/metabolism ; },
abstract = {Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron's ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated. Some claim that mutated HFE exacerbates oxidative stress and neuroinflammation, thus predisposing carriers to neurodegeneration-linked pathologies. However, H63D HFE has also been shown to slow the progression of multiple neurodegenerative diseases and to protect against environmental toxins that cause neurodegeneration. These conflicting results showcase the need to further understand the contribution of HFE variants to neurodegenerative disease heterogeneity. Data from mouse models consistently demonstrate robust neuroprotection against toxins known to increase the risk of neurodegenerative disease. This may represent an adaptive, or hormetic, response to increased iron, which leaves cells better protected against future stressors. This review describes the current research regarding the contribution of HFE variants to neurodegenerative disease prognosis in the context of a hormetic model. To our knowledge, this is the first time that a hormetic model for neurodegenerative disease has been presented.},
}

Mice
Animals
*Neurodegenerative Diseases/genetics
Hemochromatosis Protein/genetics
Histocompatibility Antigens Class I/genetics
Hormesis
Mutation
Iron/metabolism

@article {pmid38540795,
year = {2024},
author = {Gascón, E and Zaragoza, P and Calvo, AC and Osta, R},
title = {Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes.},
journal = {Biomolecules},
volume = {14},
number = {3},
pages = {},
pmid = {38540795},
issn = {2218-273X},
support = {PI17/00949//Instituto de Salud Carlos III/ ; A19_23R//"LAGENBIO GRUPO INVESTIGACION"/ ; CIBER-358 NED-612-CB18/05/00037//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; },
mesh = {Humans ; Transcriptome/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; Muscle, Skeletal/metabolism ; Biomarkers ; },
abstract = {Amyotrophic lateral sclerosis (ALS) that comprises sporadic (sALS) and familial (fALS) cases, is a devastating neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle atrophy and various clinical manifestations. However, the complex underlying mechanisms affecting this disease are not yet known. On the other hand, there is also no good prognosis of the disease due to the lack of biomarkers and therapeutic targets. Therefore, in this study, by means of bioinformatics analysis, sALS-affected muscle tissue was analyzed using the GEO GSE41414 dataset, identifying 397 differentially expressed genes (DEGs). Functional analysis revealed 320 up-regulated DEGs associated with muscle development and 77 down-regulated DEGs linked to energy metabolism. Protein-protein interaction network analysis identified 20 hub genes, including EIF4A1, HNRNPR and NDUFA4. Furthermore, miRNA target gene networks revealed 17 miRNAs linked to hub genes, with hsa-mir-206, hsa-mir-133b and hsa-mir-100-5p having been previously implicated in ALS. This study presents new potential biomarkers and therapeutic targets for ALS by correlating the information obtained with a comprehensive literature review, providing new potential targets to study their role in ALS.},
}

Humans
Transcriptome/genetics
*Amyotrophic Lateral Sclerosis/genetics/metabolism
*MicroRNAs/genetics/metabolism
Muscle, Skeletal/metabolism
Biomarkers

@article {pmid38540709,
year = {2024},
author = {Stoklund Dittlau, K and Freude, K},
title = {Astrocytes: The Stars in Neurodegeneration?.},
journal = {Biomolecules},
volume = {14},
number = {3},
pages = {},
pmid = {38540709},
issn = {2218-273X},
support = {R434-2023-242//Lundbeck Foundation/ ; 2078-00002B//Innovation Fund Denmark/ ; NNF21OC0071571//Novo Nordisk Foundation/ ; N/A//Alzheimer Foundation Denmark/ ; },
mesh = {Humans ; Astrocytes/physiology ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis/therapy ; },
abstract = {Today, neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) affect millions of people worldwide, and as the average human lifespan increases, similarly grows the number of patients. For many decades, cognitive and motoric decline has been explained by the very apparent deterioration of neurons in various regions of the brain and spinal cord. However, more recent studies show that disease progression is greatly influenced by the vast population of glial cells. Astrocytes are traditionally considered star-shaped cells on which neurons rely heavily for their optimal homeostasis and survival. Increasing amounts of evidence depict how astrocytes lose their supportive functions while simultaneously gaining toxic properties during neurodegeneration. Many of these changes are similar across various neurodegenerative diseases, and in this review, we highlight these commonalities. We discuss how astrocyte dysfunction drives neuronal demise across a wide range of neurodegenerative diseases, but rather than categorizing based on disease, we aim to provide an overview based on currently known mechanisms. As such, this review delivers a different perspective on the disease causes of neurodegeneration in the hope to encourage further cross-disease studies into shared disease mechanisms, which might ultimately disclose potentially common therapeutic entry points across a wide panel of neurodegenerative diseases.},
}

Humans
Astrocytes/physiology
*Neurodegenerative Diseases
*Alzheimer Disease
*Parkinson Disease
*Amyotrophic Lateral Sclerosis/therapy

@article {pmid38540369,
year = {2024},
author = {Souza, PVS and Serrano, PL and Farias, IB and Machado, RIL and Badia, BML and Oliveira, HB and Barbosa, AS and Pereira, CA and Moreira, VF and Chieia, MAT and Barbosa, AR and Braga, VL and Pinto, WBVR and Oliveira, ASB},
title = {Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.},
journal = {Genes},
volume = {15},
number = {3},
pages = {},
pmid = {38540369},
issn = {2073-4425},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Motor Neurons ; Neuroimaging ; },
abstract = {Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci have been associated with both sporadic and familial juvenile Amyotrophic Lateral Sclerosis. Currently, almost 40% of cases have an identifiable monogenic basis; type 6, associated with FUS gene variants, is the most prevalent globally. Despite several upper motor neuron-dominant forms being generally associated with long-standing motor symptoms and slowly progressive course, certain subtypes with lower motor neuron-dominant features and early bulbar compromise lead to rapidly progressive motor handicap. For some monogenic forms, there is a well-established genotypic-phenotypic correlation. There are no specific biochemical and neuroimaging biomarkers for the diagnosis of juvenile Amyotrophic Lateral Sclerosis. There are several inherited neurodegenerative and neurometabolic disorders which can lead to the signs of motor neuron impairment. This review emphasizes the importance of high clinical suspicion, assessment, and proper diagnostic work-up for juvenile Amyotrophic Lateral Sclerosis.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics
Motor Neurons
Neuroimaging

@article {pmid38538275,
year = {2024},
author = {Ceccarelli, L and Verriello, L and Pauletto, G and Valente, M and Spadea, L and Salati, C and Zeppieri, M and Ius, T},
title = {The Role of Human Pluripotent Stem Cells in Amyotrophic Lateral Sclerosis: From Biological Mechanism to Practical Implications.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {29},
number = {3},
pages = {114},
doi = {10.31083/j.fbl2903114},
pmid = {38538275},
issn = {2768-6698},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Motor Neurons/metabolism ; *Pluripotent Stem Cells/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism/pathology ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro, which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism
Motor Neurons/metabolism
*Pluripotent Stem Cells/metabolism/pathology
*Induced Pluripotent Stem Cells/metabolism/pathology

@article {pmid38535081,
year = {2024},
author = {Liampas, I and Danga, F and Kyriakoulopoulou, P and Siokas, V and Stamati, P and Messinis, L and Dardiotis, E and Nasios, G},
title = {The Contribution of Functional Near-Infrared Spectroscopy (fNIRS) to the Study of Neurodegenerative Disorders: A Narrative Review.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
pmid = {38535081},
issn = {2075-4418},
abstract = {Functional near-infrared spectroscopy (fNIRS) is an innovative neuroimaging method that offers several advantages over other commonly used modalities. This narrative review investigated the potential contribution of this method to the study of neurodegenerative disorders. Thirty-four studies involving patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), frontotemporal dementia (FTD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) and healthy controls were reviewed. Overall, it was revealed that the prefrontal cortex of individuals with MCI may engage compensatory mechanisms to support declining brain functions. A rightward shift was suggested to compensate for the loss of the left prefrontal capacity in the course of cognitive decline. In parallel, some studies reported the failure of compensatory mechanisms in MCI and early AD; this lack of appropriate hemodynamic responses may serve as an early biomarker of neurodegeneration. One article assessing FTD demonstrated a heterogeneous cortical activation pattern compared to AD, indicating that fNIRS may contribute to the challenging distinction of these conditions. Regarding PD, there was evidence that cognitive resources (especially executive function) were recruited to compensate for locomotor impairments. As for ALS, fNIRS data support the involvement of extra-motor networks in ALS, even in the absence of measurable cognitive impairment.},
}

@article {pmid38534355,
year = {2024},
author = {Cohen, J and Mathew, A and Dourvetakis, KD and Sanchez-Guerrero, E and Pangeni, RP and Gurusamy, N and Aenlle, KK and Ravindran, G and Twahir, A and Isler, D and Sosa-Garcia, SR and Llizo, A and Bested, AC and Theoharides, TC and Klimas, NG and Kempuraj, D},
title = {Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.},
journal = {Cells},
volume = {13},
number = {6},
pages = {},
pmid = {38534355},
issn = {2073-4409},
mesh = {Humans ; Neuroinflammatory Diseases ; Endothelial Cells ; *Induced Pluripotent Stem Cells ; *Neurodegenerative Diseases ; Inflammation ; },
abstract = {Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.},
}

Humans
Neuroinflammatory Diseases
Endothelial Cells
*Induced Pluripotent Stem Cells
*Neurodegenerative Diseases
Inflammation

@article {pmid38533300,
year = {2024},
author = {Moskvin, SV},
title = {A brief literature review of low-level laser therapy for treating amyotrophic lateral sclerosis and confirmation of its effectiveness.},
journal = {BioMedicine},
volume = {14},
number = {1},
pages = {1-9},
pmid = {38533300},
issn = {2211-8020},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a steadily progressive course due to the death of central and peripheral motor neurons responsible for voluntary movements. Low-level laser therapy (LLLT) is a treatment method unique in its universality and efficacy, particularly for neurodegenerative diseases.

METHODS: In this review, we discuss the effect and application of LLLT in the treatment of ALS. A literature search for English and Russian publications for the keywords "Amyotrophic Lateral Sclerosis", "Low-Level Laser Therapy" was performed using PubMed, Scopus, Google Scholar, Web of Science and Russian Science Citation Index (RSCI) databases.

RESULTS: The article provided a brief literature review, substantiated the potential use of low-level laser therapy for ALS. The particular techniques of LLLT were developed.

CONCLUSION: Based on the results of several studies and many years of successful experience with low-level laser therapy in Russia we conclude that a LLLT technique, including intravenous laser blood illumination (ILBI), noninvasive laser blood illumination (NLBI), and local exposure, is a promising treatment method for ALS.},
}

@article {pmid38525704,
year = {2024},
author = {Shirai, R and Yamauchi, J},
title = {Emerging Evidence of Golgi Stress Signaling for Neuropathies.},
journal = {Neurology international},
volume = {16},
number = {2},
pages = {334-348},
pmid = {38525704},
issn = {2035-8385},
abstract = {The Golgi apparatus is an intracellular organelle that modifies cargo, which is transported extracellularly through the nucleus, endoplasmic reticulum, and plasma membrane in order. First, the general function of the Golgi is reviewed and, then, Golgi stress signaling is discussed. In addition to the six main Golgi signaling pathways, two pathways that have been increasingly reported in recent years are described in this review. The focus then shifts to neurological disorders, examining Golgi stress reported in major neurological disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The review also encompasses findings related to other diseases, including hypomyelinating leukodystrophy, frontotemporal spectrum disorder/amyotrophic lateral sclerosis, microcephaly, Wilson's disease, and prion disease. Most of these neurological disorders cause Golgi fragmentation and Golgi stress. As a result, strong signals may act to induce apoptosis.},
}

@article {pmid38524401,
year = {2024},
author = {Pota, V and Sansone, P and De Sarno, S and Aurilio, C and Coppolino, F and Barbarisi, M and Barbato, F and Fiore, M and Cosenza, G and Passavanti, MB and Pace, MC},
title = {Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.},
journal = {Behavioural neurology},
volume = {2024},
number = {},
pages = {1228194},
pmid = {38524401},
issn = {1875-8584},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Pain Measurement ; Quality of Life ; *Neurodegenerative Diseases/complications ; Pain/drug therapy ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications
Pain Measurement
Quality of Life
*Neurodegenerative Diseases/complications
Pain/drug therapy

@article {pmid38517530,
year = {2024},
author = {Kotsia, E and Chroni, E and Alexandropoulou, A and Mills, C and Veltsista, D and Kefalopoulou, ZM and Michou, E},
title = {Dysphagia Assessments as Criteria in the 'Decision-Making Process' for Percutaneous Endoscopic Gastrostomy Placement in People with Amyotrophic Lateral Sclerosis: A Systematic Review.},
journal = {Dysphagia},
volume = {},
number = {},
pages = {},
pmid = {38517530},
issn = {1432-0460},
abstract = {To review the assessment methods of dysphagia as a criterion for the decision-making process for Percutaneous Endoscopic Gastrostomy (PEG) placement in patients with Amyotrophic Lateral Sclerosis (ALS). Systematic review. A search was conducted in three databases (EMBASE, CINAHL, PUBMED) in December 2022 and updated in July 2023. Two reviewers independently screened, selected, and extracted data. Study quality was appraised using the Joanna Briggs Institute Critical Appraisal Tools. Systematic review registration number in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022385461. The searches identified 240 records. The 10 eligible studies included 2 case reports, 4 retrospective studies, 3 prospective studies, and 1 cohort observational study. Study quality was low, with most studies having moderate to high risk of bias. Dysphagia is a common criterion for decision-making. Dysphagia assessment is usually in the form of either self-reports, objective instrumental assessments, or both. Dysphagia is a common criterion for the decision-making process, yet is missing in clinical guidelines. Establishing the optimal means of dysphagia assessment is important for timely decision-making procedures, so that life-threatening consequences of dysphagia are minimized.},
}

@article {pmid38516735,
year = {2024},
author = {Li, X and Bedlack, R},
title = {Evaluating emerging drugs in phase II & III for the treatment of amyotrophic lateral sclerosis.},
journal = {Expert opinion on emerging drugs},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/14728214.2024.2333420},
pmid = {38516735},
issn = {1744-7623},
abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis is a rapidly progressive motor neuron disorder causing severe disability and premature death. Owing to the advances in uncovering ALS pathophysiology, efficient clinical trial design and research advocacy program, several disease-modifying drugs have been approved for treating ALS. Despite this progress, ALS remains a rapidly disabling and life shortening condition. There is a critical need for more effective therapies.

AREAS COVERED: Here, we reviewed the emerging ALS therapeutics undergoing phase II & III clinical trials. To identify the investigational drugs, we searched ALS and phase II/III trials that are active and recruiting or not yet recruiting on clinicaltrials.gov and Pharmaprojects database.

EXPERT OPINION: The current pipeline is larger and more diverse than ever, with drugs targeting potential genetic and retroviral causes of ALS and drugs targeting a wide array of downstream pathways, including RNA metabolism, protein aggregation, integrated stress response and neuroinflammation.We remain most excited about those that target direct causes of ALS, e.g. antisense oligonucleotides targeting causative genes. Drugs that eliminate abnormal protein aggregates are also up-and-coming. Eventually, because of the heterogeneity of ALS pathophysiology, biomarkers that determine which biological events are most important for an individual ALS patient are needed.},
}

@article {pmid38515787,
year = {2024},
author = {Wang, L and Fang, X and Ling, B and Wang, F and Xia, Y and Zhang, W and Zhong, T and Wang, X},
title = {Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1359453},
pmid = {38515787},
issn = {1662-5102},
abstract = {Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.},
}

@article {pmid38514815,
year = {2024},
author = {Baxter, RC},
title = {Endocrine and cellular physiology and pathology of the insulin-like growth factor acid-labile subunit.},
journal = {Nature reviews. Endocrinology},
volume = {},
number = {},
pages = {},
pmid = {38514815},
issn = {1759-5037},
abstract = {The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1β, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states.},
}

@article {pmid38512820,
year = {2024},
author = {Bartolomé-Nafría, A and García-Pardo, J and Ventura, S},
title = {Mutations in human prion-like domains: pathogenic but not always amyloidogenic.},
journal = {Prion},
volume = {18},
number = {1},
pages = {28-39},
pmid = {38512820},
issn = {1933-690X},
mesh = {Humans ; *Prions/metabolism ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mutation ; },
abstract = {Heterogeneous nuclear ribonucleoproteins (hnRNPs) are multifunctional proteins with integral roles in RNA metabolism and the regulation of alternative splicing. These proteins typically contain prion-like domains of low complexity (PrLDs or LCDs) that govern their assembly into either functional or pathological amyloid fibrils. To date, over 60 mutations targeting the LCDs of hnRNPs have been identified and associated with a spectrum of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). The cryo-EM structures of pathological and functional fibrils formed by different hnRNPs have been recently elucidated, including those of hnRNPA1, hnRNPA2, hnRNPDL-2, TDP-43, and FUS. In this review, we discuss the structural features of these amyloid assemblies, placing particular emphasis on scrutinizing the impact of prevalent disease-associated mutations mapping within their LCDs. By performing systematic energy calculations, we reveal a prevailing trend of destabilizing effects induced by these mutations in the amyloid structure, challenging the traditionally assumed correlation between pathogenicity and amyloidogenic propensity. Understanding the molecular basis of this discrepancy might provide insights for developing targeted therapeutic strategies to combat hnRNP-associated diseases.},
}

Humans
*Prions/metabolism
*Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Frontotemporal Dementia/genetics/metabolism/pathology
Mutation

@article {pmid38510000,
year = {2024},
author = {Ditan, ID and Turalde, CWR},
title = {Treatment gaps in the care of amyotrophic lateral sclerosis in the Philippines: A scoping review.},
journal = {Heliyon},
volume = {10},
number = {6},
pages = {e27944},
pmid = {38510000},
issn = {2405-8440},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive disease affecting both the upper and lower motor neurons. Much of the management of ALS is supportive with the goal of maximizing patient quality of life. While the Philippines was participative in the "Ice Bucket Challenge" in 2014, it is up for investigation whether substantial changes occurred to improve healthcare for ALS patients. This study aims to evaluate the treatment gaps in the management of ALS in the Philippines through a scoping review. Data on epidemiology, health systems, and pharmacotherapy available regarding ALS in the local setting were synthesized. Nine articles were included. As of July 2023, there were only four indexed studies on ALS from the Philippines. Five of the included articles investigated ALS in Filipino populations but were not authored by Filipinos nor affiliated with Philippine institutions. The available literature showed a distinct lack of local ALS epidemiologic data, as well as limited availability in diagnostic centers, medications, health financing options, and digestible information for Filipinos. The limitations in managing ALS in the country are multifactorial - from political, medical, and social. It is imperative to establish a national database, financing systems, support groups, and accessible diagnostic centers for ALS patients.},
}

@article {pmid38500677,
year = {2024},
author = {Zhou, L and Xu, R},
title = {Invertebrate genetic models of amyotrophic lateral sclerosis.},
journal = {Frontiers in molecular neuroscience},
volume = {17},
number = {},
pages = {1328578},
pmid = {38500677},
issn = {1662-5099},
abstract = {Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by the progressive death of motor neurons in the cerebral cortex, brain stem, and spinal cord. The exact mechanisms underlying the pathogenesis of ALS remain unclear. The current consensus regarding the pathogenesis of ALS suggests that the interaction between genetic susceptibility and harmful environmental factors is a promising cause of ALS onset. The investigation of putative harmful environmental factors has been the subject of several ongoing studies, but the use of transgenic animal models to study ALS has provided valuable information on the onset of ALS. Here, we review the current common invertebrate genetic models used to study the pathology, pathophysiology, and pathogenesis of ALS. The considerations of the usage, advantages, disadvantages, costs, and availability of each invertebrate model will also be discussed.},
}

@article {pmid38499161,
year = {2024},
author = {Bashir, S and Aiman, A and Shahid, M and Chaudhary, AA and Sami, N and Basir, SF and Hassan, I and Islam, A},
title = {Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.},
journal = {Ageing research reviews},
volume = {96},
number = {},
pages = {102276},
doi = {10.1016/j.arr.2024.102276},
pmid = {38499161},
issn = {1872-9649},
mesh = {Humans ; Amyloid/metabolism ; *Amyloidosis/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/metabolism ; Amyloidogenic Proteins ; Perception ; },
abstract = {Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.},
}

Humans
Amyloid/metabolism
*Amyloidosis/metabolism
*Neurodegenerative Diseases/metabolism
*Parkinson Disease/metabolism
Amyloidogenic Proteins
Perception

@article {pmid38498721,
year = {2024},
author = {Kertesz, A and Finger, E and Munoz, DG},
title = {Progress in Primary Progressive Aphasia: A Review.},
journal = {Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology},
volume = {37},
number = {1},
pages = {3-12},
pmid = {38498721},
issn = {1543-3641},
mesh = {Humans ; *Frontotemporal Dementia/diagnosis/genetics ; *Supranuclear Palsy, Progressive/genetics/pathology ; Syndrome ; *Aphasia, Primary Progressive ; },
abstract = {We present a review of the definition, classification, and epidemiology of primary progressive aphasia (PPA); an update of the taxonomy of the clinical syndrome of PPA; and recent advances in the neuroanatomy, pathology, and genetics of PPA, as well as the search for biomarkers and treatment. PPA studies that have contributed to concepts of language organization and disease propagation in neurodegeneration are also reviewed. In addition, the issues of heterogeneity versus the relationships of the clinical phenotypes and their relationship to biological, pathological, and genetic advances are discussed, as is PPA's relationship to other conditions such as frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, Pick disease, and amyotrophic lateral sclerosis. Arguments are presented in favor of considering these conditions as one entity versus many.},
}

Humans
*Frontotemporal Dementia/diagnosis/genetics
*Supranuclear Palsy, Progressive/genetics/pathology
Syndrome
*Aphasia, Primary Progressive

@article {pmid38490348,
year = {2024},
author = {Chatterjee, A and Kumar, S and Roy Sarkar, S and Halder, R and Kumari, R and Banerjee, S and Sarkar, B},
title = {Dietary polyphenols represent a phytotherapeutic alternative for gut dysbiosis associated neurodegeneration: A systematic review.},
journal = {The Journal of nutritional biochemistry},
volume = {129},
number = {},
pages = {109622},
doi = {10.1016/j.jnutbio.2024.109622},
pmid = {38490348},
issn = {1873-4847},
abstract = {Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention. Numerous studies lend credence to the notion that changes in the intestinal microbiota and enteric neuroimmune system have an impact on the initiation and severity of these diseases. The prebiotic role of polyphenols can influence the makeup of the gut microbiota in neurodegenerative disorders by modulating intracellular signalling pathways. Metabolites of polyphenols function directly as neurotransmitters by crossing the blood-brain barrier or indirectly via influencing the cerebrovascular system. This assessment aims to bring forth an interlink between the consumption of polyphenols biotransformed by gut microbiota which in turn modulate the gut microbial diversity and biochemical changes in the brain. This systematic review will further augment research towards the association of dietary polyphenols in the management of gut dysbiosis-associated neurodegenerative diseases.},
}

@article {pmid38489867,
year = {2024},
author = {Tausendfreund, O and Bidlingmaier, M and Martini, S and Müller, K and Rippl, M and Schilbach, K and Schmidmaier, R and Drey, M},
title = {Growth hormone treatment in aged patients with comorbidities: A systematic review.},
journal = {Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society},
volume = {75},
number = {},
pages = {101584},
doi = {10.1016/j.ghir.2024.101584},
pmid = {38489867},
issn = {1532-2238},
mesh = {Aged ; Humans ; Comorbidity ; Growth Hormone ; *Human Growth Hormone/adverse effects/therapeutic use ; Insulin-Like Growth Factor I ; Quality of Life ; Randomized Controlled Trials as Topic ; *Aging/pathology ; },
abstract = {OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects.

DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library.

INCLUSION CRITERIA: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis.

RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life.

CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.},
}

Aged
Humans
Comorbidity
Growth Hormone
*Human Growth Hormone/adverse effects/therapeutic use
Insulin-Like Growth Factor I
Quality of Life
Randomized Controlled Trials as Topic
*Aging/pathology

@article {pmid38483631,
year = {2024},
author = {Perera, A and Brock, O and Ahmed, A and Shaw, C and Ashkan, K},
title = {Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS.},
journal = {Acta neurochirurgica},
volume = {166},
number = {1},
pages = {136},
pmid = {38483631},
issn = {0942-0940},
mesh = {Humans ; *Central Nervous System ; Genetic Therapy/methods ; Genetic Vectors ; *Neurodegenerative Diseases/genetics/therapy ; },
abstract = {Gene supplementation and editing for neurodegenerative disorders has emerged in recent years as the understanding of the genetic mechanisms underlying several neurodegenerative disorders increases. The most common medium to deliver genetic material to cells is via viral vectors; and with respect to the central nervous system, adeno-associated viral (AAV) vectors are a popular choice. The most successful example of AAV-based gene therapy for neurodegenerative disorders is Zolgensma© which is a transformative intravenous therapy given to babies with spinal muscular atrophy. However, the field has stalled in achieving safe drug delivery to the central nervous system in adults for which treatments for disorders such as amyotrophic lateral sclerosis are desperately needed. Surgical gene therapy delivery has been proposed as a potential solution to this problem. While the field of the so-called regenerative neurosurgery has yielded pre-clinical optimism, several challenges have emerged. This review seeks to explore the field of regenerative neurosurgery with respect to AAV-based gene therapy for neurodegenerative diseases, its progress so far and the challenges that need to be overcome.},
}

Humans
*Central Nervous System
Genetic Therapy/methods
Genetic Vectors
*Neurodegenerative Diseases/genetics/therapy

@article {pmid38477419,
year = {2024},
author = {de Fátima Dos Santos Sampaio, M and de Paiva, YB and Sampaio, TB and Pereira, MG and Coimbra, NC},
title = {Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.},
journal = {Basic & clinical pharmacology & toxicology},
volume = {134},
number = {5},
pages = {574-601},
doi = {10.1111/bcpt.13997},
pmid = {38477419},
issn = {1742-7843},
support = {2014/11869-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2020/15050-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; PDJ grant 155489/2018-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; Research Grant (NAP-USP-NuPNE; process IaPq2012-15//Universidade de São Paulo/ ; 374/2022//Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo/ ; 302605/2021-5//CNPq/ ; 301341/2015-0//CNPq/ ; 301905/2010-0//CNPq/ ; 155489/2018-6//CNPq/ ; },
mesh = {Humans ; *Cannabidiol/pharmacology/therapeutic use ; *Parkinson Disease/drug therapy ; *Multiple Sclerosis/drug therapy ; Receptor, Serotonin, 5-HT1A/therapeutic use ; *Cannabinoids/pharmacology/therapeutic use ; *Epilepsy/drug therapy ; *Mental Disorders/drug therapy ; Comorbidity ; },
abstract = {Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.},
}

Humans
*Cannabidiol/pharmacology/therapeutic use
*Parkinson Disease/drug therapy
*Multiple Sclerosis/drug therapy
Receptor, Serotonin, 5-HT1A/therapeutic use
*Cannabinoids/pharmacology/therapeutic use
*Epilepsy/drug therapy
*Mental Disorders/drug therapy
Comorbidity

@article {pmid38474719,
year = {2024},
author = {Noor Eddin, A and Alfuwais, M and Noor Eddin, R and Alkattan, K and Yaqinuddin, A},
title = {Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.},
journal = {Nutrients},
volume = {16},
number = {5},
pages = {},
pmid = {38474719},
issn = {2072-6643},
mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Dysbiosis/etiology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Disease Progression ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients. These changes are often correlated with disease progression and patient outcome, suggesting that GBA modulation may have therapeutic potential. Indeed, targeting the gut microbiota has been shown to be neuroprotective in several animal models, alleviating motor symptoms and mitigating disease progression. However, the translation of these findings to human patients is challenging due to the complexity of ALS pathology and the varying diversity of gut microbiota. This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction. It delineates three main mechanisms by which dysbiosis contributes to ALS pathology: compromised intestinal barrier integrity, metabolic dysfunction, and immune dysregulation. It also examines preclinical evidence on the therapeutic potential of gut-microbiota-modulating agents (categorized as prebiotics, probiotics, and postbiotics) in ALS.},
}

Animals
Humans
*Amyotrophic Lateral Sclerosis/pathology
Dysbiosis/etiology
*Gastrointestinal Microbiome/physiology
*Microbiota
Disease Progression

@article {pmid38474416,
year = {2024},
author = {Tzeplaeff, L and Jürs, AV and Wohnrade, C and Demleitner, AF},
title = {Unraveling the Heterogeneity of ALS-A Call to Redefine Patient Stratification for Better Outcomes in Clinical Trials.},
journal = {Cells},
volume = {13},
number = {5},
pages = {},
pmid = {38474416},
issn = {2073-4409},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Treatment Outcome ; Clinical Trials as Topic ; },
abstract = {Despite tremendous efforts in basic research and a growing number of clinical trials aiming to find effective treatments, amyotrophic lateral sclerosis (ALS) remains an incurable disease. One possible reason for the lack of effective causative treatment options is that ALS may not be a single disease entity but rather may represent a clinical syndrome, with diverse genetic and molecular causes, histopathological alterations, and subsequent clinical presentations contributing to its complexity and variability among individuals. Defining a way to subcluster ALS patients is becoming a central endeavor in the field. Identifying specific clusters and applying them in clinical trials could enable the development of more effective treatments. This review aims to summarize the available data on heterogeneity in ALS with regard to various aspects, e.g., clinical, genetic, and molecular.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology
Treatment Outcome
Clinical Trials as Topic

@article {pmid38474399,
year = {2024},
author = {Manora, L and Borlongan, CV and Garbuzova-Davis, S},
title = {Cellular and Noncellular Approaches for Repairing the Damaged Blood-CNS-Barrier in Amyotrophic Lateral Sclerosis.},
journal = {Cells},
volume = {13},
number = {5},
pages = {},
pmid = {38474399},
issn = {2073-4409},
support = {R01 NS090962/NS/NINDS NIH HHS/United States ; R21 NS132576/NS/NINDS NIH HHS/United States ; 1R21NS132576-01/NS/NINDS NIH HHS/United States ; 1R01NS090962/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Endothelial Cells/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Stem Cells/metabolism ; },
abstract = {Numerous reports have demonstrated the breakdown of the blood-CNS barrier (B-CNS-B) in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Re-establishing barrier integrity in the CNS is critical to prevent further motor neuron degeneration from harmful components in systemic circulation. Potential therapeutic strategies for repairing the B-CNS-B may be achieved by the replacement of damaged endothelial cells (ECs) via stem cell administration or enhancement of endogenous EC survival through the delivery of bioactive particles secreted by stem cells. These cellular and noncellular approaches are thoroughly discussed in the present review. Specific attention is given to certain stem cell types for EC replacement. Also, various nanoparticles secreted by stem cells as well as other biomolecules are elucidated as promising agents for endogenous EC repair. Although the noted in vitro and in vivo studies show the feasibility of the proposed therapeutic approaches to the repair of the B-CNS-B in ALS, further investigation is needed prior to clinical transition.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism
Endothelial Cells/metabolism
*Neurodegenerative Diseases/metabolism
Motor Neurons/metabolism
Stem Cells/metabolism

@article {pmid38474192,
year = {2024},
author = {Yamashita, T and Abe, K},
title = {Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {5},
pages = {},
pmid = {38474192},
issn = {1422-0067},
support = {23K08543, 21K19572//Grant-in-Aid for Scientific Research/ ; },
mesh = {Animals ; Female ; Pregnancy ; *Amyotrophic Lateral Sclerosis/drug therapy ; Antioxidants/therapeutic use ; Antipyrine ; Edaravone/pharmacology/therapeutic use ; Free Radical Scavengers/pharmacology ; *Neurodegenerative Diseases/drug therapy ; *Neuroprotective Agents/pharmacology ; Placenta ; },
abstract = {The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.},
}

Animals
Female
Pregnancy
*Amyotrophic Lateral Sclerosis/drug therapy
Antioxidants/therapeutic use
Antipyrine
Edaravone/pharmacology/therapeutic use
Free Radical Scavengers/pharmacology
*Neurodegenerative Diseases/drug therapy
*Neuroprotective Agents/pharmacology
Placenta

@article {pmid38473944,
year = {2024},
author = {Scarian, E and Viola, C and Dragoni, F and Di Gerlando, R and Rizzo, B and Diamanti, L and Gagliardi, S and Bordoni, M and Pansarasa, O},
title = {New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {5},
pages = {},
pmid = {38473944},
issn = {1422-0067},
support = {Ricerca Corrente 2022-2024//Ministero della Salute/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Oxidative Stress/physiology ; Antioxidants/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Inflammation/drug therapy ; },
abstract = {Oxidative stress (OS) and inflammation are two important and well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence of easily oxidizable polyunsaturated fatty acids and the weak antioxidant defenses, the brain is particularly vulnerable to oxidative injury. Uncertainty exists over whether these deficits contribute to the development of NDDs or are solely a consequence of neuronal degeneration. Furthermore, these two pathological hallmarks are linked, and it is known that OS can affect the inflammatory response. In this review, we will overview the last findings about these two pathways in the principal NDDs. Moreover, we will focus more in depth on amyotrophic lateral sclerosis (ALS) to understand how anti-inflammatory and antioxidants drugs have been used for the treatment of this still incurable motor neuron (MN) disease. Finally, we will analyze the principal past and actual clinical trials and the future perspectives in the study of these two pathological mechanisms.},
}

Humans
*Neurodegenerative Diseases/metabolism
Oxidative Stress/physiology
Antioxidants/metabolism
*Amyotrophic Lateral Sclerosis/metabolism
Inflammation/drug therapy

@article {pmid38463392,
year = {2024},
author = {Chen, Y and Mateski, J and Gerace, L and Wheeler, J and Burl, J and Prakash, B and Svedin, C and Amrick, R and Adams, BD},
title = {Non-coding RNAs and neuroinflammation: implications for neurological disorders.},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {249},
number = {},
pages = {10120},
pmid = {38463392},
issn = {1535-3699},
mesh = {Humans ; Neuroinflammatory Diseases ; *Nervous System Diseases/genetics ; Microglia/metabolism ; *MicroRNAs/genetics/metabolism ; Cytokines/metabolism ; Chemokines/metabolism ; },
abstract = {Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, or infection, persistent neuroinflammation results in a heightened presence of cytokines, chemokines, and reactive oxygen species that result in tissue damage. In the CNS, the surrounding microglia normally contain macrophages and other innate immune cells that perform active immune surveillance. The resulting cytokines produced by these macrophages affect the growth, development, and responsiveness of the microglia present in both white and gray matter regions of the CNS. Controlling the levels of these cytokines ultimately improves neurocognitive function and results in the repair of lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators of the genome and subsequently control the activity of inflammatory responses crucial in sustaining a robust and acute immunological response towards an acute infection while dampening pathways that result in heightened levels of cytokines and chemokines associated with chronic neuroinflammation. Numerous reports have directly implicated miRNAs in controlling the abundance and activity of interleukins, TGF-B, NF-kB, and toll-like receptor-signaling intrinsically linked with the development of neurological disorders such as Parkinson's, ALS, epilepsy, Alzheimer's, and neuromuscular degeneration. This review is focused on discussing the role miRNAs play in regulating or initiating these chronic neurological states, many of which maintain the level and/or activity of neuron-specific secondary messengers. Dysregulated miRNAs present in the microglia, astrocytes, oligodendrocytes, and epididymal cells, contribute to an overall glial-specific inflammatory niche that impacts the activity of neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, and neuron-muscular connections. Understanding which miRNAs regulate microglial activation is a crucial step forward in developing non-coding RNA-based therapeutics to treat and potentially correct the behavioral and cognitive deficits typically found in patients suffering from chronic neuroinflammation.},
}

Humans
Neuroinflammatory Diseases
*Nervous System Diseases/genetics
Microglia/metabolism
*MicroRNAs/genetics/metabolism
Cytokines/metabolism
Chemokines/metabolism

@article {pmid38452377,
year = {2024},
author = {Rajabi, D and Khanmohammadi, S and Rezaei, N},
title = {The role of long noncoding RNAs in amyotrophic lateral sclerosis.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {38452377},
issn = {2191-0200},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.},
}

@article {pmid38430933,
year = {2024},
author = {Li, D and Zhou, L and Cao, Z and Wang, J and Yang, H and Lyu, M and Zhang, Y and Yang, R and Wang, J and Bian, Y and Xu, W and Wang, Y},
title = {Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.},
journal = {Ageing research reviews},
volume = {95},
number = {},
pages = {102254},
doi = {10.1016/j.arr.2024.102254},
pmid = {38430933},
issn = {1872-9649},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Exposome ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Multiple Sclerosis/genetics ; },
abstract = {Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Exposome
Genome-Wide Association Study
Mendelian Randomization Analysis
*Alzheimer Disease/genetics
*Parkinson Disease
*Multiple Sclerosis/genetics

@article {pmid38430277,
year = {2024},
author = {Jagaraj, CJ and Shadfar, S and Kashani, SA and Saravanabavan, S and Farzana, F and Atkin, JD},
title = {Molecular hallmarks of ageing in amyotrophic lateral sclerosis.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {81},
number = {1},
pages = {111},
pmid = {38430277},
issn = {1420-9071},
support = {1095215//National Institute for Dementia Research/ ; Peter Stearne Familial MND Research Grant//Motor Neurone Disease Australia/ ; Linda Rynalski Bridge Funding Grant//Motor Neurone Disease Australia/ ; 51909/00//FightMND/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Longevity ; Autophagy/genetics ; Brain ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, and spinal cord. Unfortunately, there are few effective treatments, thus there remains a critical need to find novel interventions that can mitigate against its effects. Whilst the aetiology of ALS remains unclear, ageing is the major risk factor. Ageing is a slowly progressive process marked by functional decline of an organism over its lifespan. However, it remains unclear how ageing promotes the risk of ALS. At the molecular and cellular level there are specific hallmarks characteristic of normal ageing. These hallmarks are highly inter-related and overlap significantly with each other. Moreover, whilst ageing is a normal process, there are striking similarities at the molecular level between these factors and neurodegeneration in ALS. Nine ageing hallmarks were originally proposed: genomic instability, loss of telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, stem cell exhaustion, and altered inter-cellular communication. However, these were recently (2023) expanded to include dysregulation of autophagy, inflammation and dysbiosis. Hence, given the latest updates to these hallmarks, and their close association to disease processes in ALS, a new examination of their relationship to pathophysiology is warranted. In this review, we describe possible mechanisms by which normal ageing impacts on neurodegenerative mechanisms implicated in ALS, and new therapeutic interventions that may arise from this.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
Longevity
Autophagy/genetics
Brain

@article {pmid38429818,
year = {2024},
author = {Darabi, S and Ariaei, A and Rustamzadeh, A and Afshari, D and Charkhat Gorgich, EA and Darabi, L},
title = {Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review.},
journal = {Diagnostic pathology},
volume = {19},
number = {1},
pages = {47},
pmid = {38429818},
issn = {1746-1596},
mesh = {Humans ; *Exosomes ; *Amyotrophic Lateral Sclerosis/diagnosis ; Superoxide Dismutase-1 ; Biomarkers ; DNA-Binding Proteins ; Disease Progression ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.

METHODS: PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.

RESULTS: A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.

CONCLUSION: Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.},
}

Humans
*Exosomes
*Amyotrophic Lateral Sclerosis/diagnosis
Superoxide Dismutase-1
Biomarkers
DNA-Binding Proteins
Disease Progression

@article {pmid38429379,
year = {2024},
author = {de Luzy, IR and Lee, MK and Mobley, WC and Studer, L},
title = {Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration.},
journal = {Nature aging},
volume = {4},
number = {3},
pages = {309-318},
pmid = {38429379},
issn = {2662-8465},
support = {ASAP-020370//Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)/ ; },
mesh = {Humans ; *Neurodegenerative Diseases ; Aging ; Cellular Senescence/physiology ; Neurons ; *Pluripotent Stem Cells ; },
abstract = {Age remains the central risk factor for many neurodegenerative diseases including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Although the mechanisms of aging are complex, the age-related accumulation of senescent cells in neurodegeneration is well documented and their clearance can alleviate disease-related features in preclinical models. Senescence-like characteristics are observed in both neuronal and glial lineages, but their relative contribution to aging and neurodegeneration remains unclear. Human pluripotent stem cell-derived neurons provide an experimental model system to induce neuronal senescence. However, the extensive heterogeneity in the profile of senescent neurons and the methods to assess senescence remain major challenges. Here, we review the evidence of cellular senescence in neuronal aging and disease, discuss human pluripotent stem cell-based model systems used to investigate neuronal senescence and propose a panel of cellular and molecular hallmarks to characterize senescent neurons. Understanding the role of neuronal senescence may yield novel therapeutic opportunities in neurodegenerative disease.},
}

Humans
*Neurodegenerative Diseases
Aging
Cellular Senescence/physiology
Neurons
*Pluripotent Stem Cells

@article {pmid38428126,
year = {2024},
author = {Wahbeh, F and Restifo, D and Laws, S and Pawar, A and Parikh, NS},
title = {Impact of tobacco smoking on disease-specific outcomes in common neurological disorders: A scoping review.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {122},
number = {},
pages = {10-18},
pmid = {38428126},
issn = {1532-2653},
support = {K23 AG073524/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Smoking Cessation ; Smoking/adverse effects/epidemiology ; Tobacco Smoking ; *Stroke/epidemiology/etiology/therapy ; *Multiple Sclerosis ; },
abstract = {Although the association of smoking with the risk of incident neurological disorders is well established, less is known about the impact of smoking and smoking cessation on outcomes of these conditions. The objective of this scoping review was to synthesize what is known about the impact of smoking and smoking cessation on disease-specific outcomes for seven common neurological disorders. We included 67 studies on the association of smoking and smoking cessation on disease-specific outcomes. For multiple sclerosis, smoking was associated with greater clinical and radiological disease progression, relapses, risk for disease-related death, cognitive decline, and mood symptoms, in addition to reduced treatment effectiveness. For stroke and transient ischemic attack, smoking was associated with greater rates of stroke recurrence, post-stroke cardiovascular outcomes, post-stroke mortality, post-stroke cognitive impairment, and functional impairment. In patients with cognitive impairment and dementia, smoking was associated with faster cognitive decline, and smoking was also associated with greater cognitive decline in Parkinson's disease, but not motor symptom worsening. Patients with amyotrophic lateral sclerosis who smoked faced increased mortality. Last, in patients with cluster headache, smoking was associated with more frequent and longer cluster attack periods. Conversely, for multiple sclerosis and stroke, smoking cessation was associated with improved disease-specific outcomes. In summary, whereas smoking is detrimentally associated with disease-specific outcomes in common neurological conditions, there is growing evidence that smoking cessation may improve outcomes. Effective smoking cessation interventions should be leveraged in the management of common neurological disorders to improve patient outcomes.},
}

Humans
*Smoking Cessation
Smoking/adverse effects/epidemiology
Tobacco Smoking
*Stroke/epidemiology/etiology/therapy
*Multiple Sclerosis

@article {pmid38417517,
year = {2024},
author = {Li, M and Qiu, J and Yan, G and Zheng, X and Li, A},
title = {How does the neurotoxin β-N-methylamino-L-alanine exist in biological matrices and cause toxicity?.},
journal = {The Science of the total environment},
volume = {922},
number = {},
pages = {171255},
doi = {10.1016/j.scitotenv.2024.171255},
pmid = {38417517},
issn = {1879-1026},
mesh = {Animals ; Humans ; *Neurotoxins/chemistry ; *Amino Acids, Diamino/toxicity/chemistry ; Cyanobacteria Toxins ; Oxidative Stress ; },
abstract = {The neurotoxin β-N-methylamino-L-alanine (BMAA) has been deemed as a risk factor for some neurodegenerative diseases such as amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC). This possible link has been proved in some primate models and cell cultures with the appearance that BMAA exposure can cause excitotoxicity, formation of protein aggregates, and/or oxidative stress. The neurotoxin BMAA extensively exists in the environment and can be transferred through the food web to human beings. In this review, the occurrence, toxicological mechanisms, and characteristics of BMAA were comprehensively summarized, and proteins and peptides were speculated as its possible binding substances in biological matrices. It is difficult to compare the published data from previous studies due to the inconsistent analytical methods and components of BMAA. The binding characteristics of BMAA should be focused on to improve our understanding of its health risk to human health in the future.},
}

Animals
Humans
*Neurotoxins/chemistry
*Amino Acids, Diamino/toxicity/chemistry
Cyanobacteria Toxins
Oxidative Stress

@article {pmid38415696,
year = {2024},
author = {Didcote, L and Vitoratou, S and Al-Chalabi, A and Goldstein, LH},
title = {What is the extent of reliability and validity evidence for screening tools for cognitive and behavioral change in people with ALS? A systematic review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-15},
pmid = {38415696},
issn = {2167-9223},
abstract = {Objective: This systematic review provides an updated summary of the existing literature on the validity of screening tools for cognitive and behavioral impairment in people with Amyotrophic Lateral Sclerosis (pwALS), and also focuses on their reliability. Method: The following cognitive and behavioral screening tools were assessed in this review: the Edinburgh Cognitive and Behavioral ALS Screen (ECAS); the ALS Cognitive Behavioral Screen (ALS-CBS), the Mini Addenbrooke's Cognitive Examination (Mini-ACE), the Beaumont Behavioral Interview (BBI); the MND Behavior Scale (MiND-B); and the ALS-FTD Questionnaire (ALS-FTD-Q). A search, using Medline, PsychINFO and Embase (21/09/2023), generated 37 results after exclusion criteria were applied. Evidence of internal consistency, item-total correlations, inter-rater reliability, clinical validity, convergent validity, and structural validity were extracted and assessed and risk of bias was evaluated. Results: The cognitive component of the ECAS was the tool with most evidence of reliability and validity for the assessment of cognitive impairment in ALS. It is well-suited to accommodate physical symptoms of ALS. For behavioral assessment, the BBI or ALS-FTD-Q had the most evidence of reliability and validity. The BBI is more thorough, but the ALS-FTD-Q is briefer. Conclusions: There is good but limited evidence for the reliability and validity of cognitive and behavioral screens. Further evidence of clinical and convergent validity would increase confidence in their clinical and research use.},
}

@article {pmid38414054,
year = {2024},
author = {Ma, YY and Li, X and Yu, JT and Wang, YJ},
title = {Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.},
journal = {Translational neurodegeneration},
volume = {13},
number = {1},
pages = {12},
pmid = {38414054},
issn = {2047-9158},
support = {92249305//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease/therapy ; },
abstract = {The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome-brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.},
}

Humans
*Neurodegenerative Diseases/therapy
*Gastrointestinal Microbiome
*Amyotrophic Lateral Sclerosis
*Alzheimer Disease
*Parkinson Disease/therapy

@article {pmid38411425,
year = {2024},
author = {D'Urso, B and Weil, R and Génin, P},
title = {[Optineurin and mitochondrial dysfunction in neurodegeneration].},
journal = {Medecine sciences : M/S},
volume = {40},
number = {2},
pages = {167-175},
doi = {10.1051/medsci/2023220},
pmid = {38411425},
issn = {1958-5381},
mesh = {Humans ; Ubiquitin ; *Amyotrophic Lateral Sclerosis/genetics ; Cytosol ; Mitochondria/genetics ; *Mitochondrial Diseases ; },
abstract = {Optineurin (OPTN) is a multifunctional protein playing a crucial role as a receptor in selective autophagy. OPTN gene mutations are linked to diseases such as normal-tension glaucoma and amyotrophic lateral sclerosis. Recognized as a critical receptor for mitophagy, OPTN is pivotal in selectively degrading damaged mitochondria. This process is essential to prevent their accumulation, the generation of reactive oxygen species, and the release of pro-apoptotic factors. Mitophagy's quality control is governed by the PINK1 kinase and the cytosolic ubiquitin ligase Parkin, whose mutations are associated with Parkinson's disease. This review highlights recent insights emphasizing OPTN's role in mitophagy and its potential involvement in neurodegenerative diseases.},
}

Humans
Ubiquitin
*Amyotrophic Lateral Sclerosis/genetics
Cytosol
Mitochondria/genetics
*Mitochondrial Diseases

@article {pmid38411261,
year = {2024},
author = {Sakowski, SA and Koubek, EJ and Chen, KS and Goutman, SA and Feldman, EL},
title = {Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions.},
journal = {Annals of neurology},
volume = {95},
number = {4},
pages = {635-652},
pmid = {38411261},
issn = {1531-8249},
support = {R01TS000327/CC/CDC HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; K23ES027221/NH/NIH HHS/United States ; R01TS000289/CC/CDC HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Exposome ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; },
abstract = {Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes are multifactorial and complex, and increasing evidence suggests a dynamic interplay between genes and the environment, emphasizing the importance of identifying and understanding the role of lifelong exposures, known as the exposome, on the nervous system. This review provides an overview of recent advances toward defining neurodegenerative disease exposomes, focusing on Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We present the current state of the field based on emerging data, elaborate on key themes and potential mechanisms, and conclude with limitations and future directions. ANN NEUROL 2024;95:635-652.},
}

Humans
*Neurodegenerative Diseases/genetics
*Exposome
*Alzheimer Disease/genetics
*Parkinson Disease/genetics

@article {pmid38401571,
year = {2024},
author = {Cheng, F and Chapman, T and Zhang, S and Morsch, M and Chung, R and Lee, A and Rayner, SL},
title = {Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease.},
journal = {Ageing research reviews},
volume = {96},
number = {},
pages = {102246},
doi = {10.1016/j.arr.2024.102246},
pmid = {38401571},
issn = {1872-9649},
mesh = {Humans ; RNA Splicing ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics ; DNA-Binding Proteins/genetics/metabolism ; Neurons/metabolism ; },
abstract = {TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circular RNA. These changes can result in the generation of an altered transcriptome and proteome within cells, ultimately changing the diversity and quantity of gene products. In this review, we summarise the findings of novel atypical RNAs resulting from TDP-43 dysfunction and their potential as biomarkers or targets for therapeutic development.},
}

Humans
RNA Splicing
*Amyotrophic Lateral Sclerosis/genetics/metabolism
*Frontotemporal Dementia/genetics
DNA-Binding Proteins/genetics/metabolism
Neurons/metabolism

@article {pmid38401191,
year = {2024},
author = {Lemon, R},
title = {The Corticospinal System and Amyotrophic Lateral Sclerosis: IFCN handbook chapter.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {160},
number = {},
pages = {56-67},
doi = {10.1016/j.clinph.2024.02.001},
pmid = {38401191},
issn = {1872-8952},
mesh = {Animals ; Humans ; *Pyramidal Tracts/physiology ; *Amyotrophic Lateral Sclerosis ; Motor Neurons/physiology ; Primates ; Axons ; },
abstract = {Corticospinal neurons located in motor areas of the cerebral neocortex project corticospinal axons which synapse with the spinal network; a parallel corticobulbar system projects to the cranial motor network and to brainstem motor pathways. The primate corticospinal system has a widespread cortical origin and an extensive range of different fibre diameters, including thick, fast-conducting axons. Direct cortico-motoneuronal (CM) projections from the motor cortex to arm and hand alpha motoneurons are a recent evolutionary feature, that is well developed in dexterous primates and particularly in humans. Many of these projections originate from the caudal subdivision of area 4 ('new' M1: primary motor cortex). They arise from corticospinal neurons of varied soma size, including those with fast- and relatively slow-conducting axons. This CM system has been shown to be involved in the control of skilled movements, carried out with fractionation of the distal extremities and at low force levels. During movement, corticospinal neurons are activated quite differently from 'lower' motoneurons, and there is no simple or fixed functional relationship between a so-called 'upper' motoneuron and its target lower motoneuron. There are key differences in the organisation and function of the corticospinal and CM system in primates versus non-primates, such as rodents. These differences need to be recognized when making the choice of animal model for understanding disorders such as amyotrophic lateral sclerosis (ALS). In this neurodegenerative brain disease there is a selective loss of fast-conducting corticospinal axons, and their synaptic connections, and this is reflected in responses to non-invasive cortical stimuli and measures of cortico-muscular coherence. The loss of CM connections influencing distal limb muscles results in a differential loss of muscle strength or 'split-hand' phenotype. Importantly, there is also a unique impairment in the coordination of skilled hand tasks that require fractionation of digit movement. Scores on validated tests of skilled hand function could be used to assess disease progression.},
}

Animals
Humans
*Pyramidal Tracts/physiology
*Amyotrophic Lateral Sclerosis
Motor Neurons/physiology
Primates
Axons

@article {pmid38399458,
year = {2024},
author = {Al Shaer, D and Al Musaimi, O and Albericio, F and de la Torre, BG},
title = {2023 FDA TIDES (Peptides and Oligonucleotides) Harvest.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {2},
pages = {},
pmid = {38399458},
issn = {1424-8247},
abstract = {A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.},
}

@article {pmid38399373,
year = {2024},
author = {Cha, Y and Kagalwala, MN and Ross, J},
title = {Navigating the Frontiers of Machine Learning in Neurodegenerative Disease Therapeutics.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {2},
pages = {},
pmid = {38399373},
issn = {1424-8247},
abstract = {Recent advances in machine learning hold tremendous potential for enhancing the way we develop new medicines. Over the years, machine learning has been adopted in nearly all facets of drug discovery, including patient stratification, lead discovery, biomarker development, and clinical trial design. In this review, we will discuss the latest developments linking machine learning and CNS drug discovery. While machine learning has aided our understanding of chronic diseases like Alzheimer's disease and Parkinson's disease, only modest effective therapies currently exist. We highlight promising new efforts led by academia and emerging biotech companies to leverage machine learning for exploring new therapies. These approaches aim to not only accelerate drug development but to improve the detection and treatment of neurodegenerative diseases.},
}

@article {pmid38397838,
year = {2024},
author = {Peggion, C and Calì, T and Brini, M},
title = {Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {38397838},
issn = {2076-3921},
abstract = {Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these diseases commonly feature chronic neuroinflammation as a hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction and protein aggregation can mutually contribute to the activation of neuroinflammatory response and thus to the onset and progression of these disorders. In the present review, we discuss the contribution of mitochondria dysfunction and neuroinflammation to the aetiology and progression of NDs, highlighting the possibility that new potential therapeutic targets can be identified to tackle neurodegenerative processes and alleviate the progression of these pathologies.},
}

@article {pmid38396996,
year = {2024},
author = {Firdaus, Z and Li, X},
title = {Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.},
journal = {International journal of molecular sciences},
volume = {25},
number = {4},
pages = {},
pmid = {38396996},
issn = {1422-0067},
support = {R01 DK129241 and DK126662/NH/NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy/pathology ; *Parkinson Disease/genetics/therapy/pathology ; *Alzheimer Disease/pathology ; *Amyotrophic Lateral Sclerosis/genetics ; },
abstract = {Genetic abnormalities play a crucial role in the development of neurodegenerative disorders (NDDs). Genetic exploration has indeed contributed to unraveling the molecular complexities responsible for the etiology and progression of various NDDs. The intricate nature of rare and common variants in NDDs contributes to a limited understanding of the genetic risk factors associated with them. Advancements in next-generation sequencing have made whole-genome sequencing and whole-exome sequencing possible, allowing the identification of rare variants with substantial effects, and improving the understanding of both Mendelian and complex neurological conditions. The resurgence of gene therapy holds the promise of targeting the etiology of diseases and ensuring a sustained correction. This approach is particularly enticing for neurodegenerative diseases, where traditional pharmacological methods have fallen short. In the context of our exploration of the genetic epidemiology of the three most prevalent NDDs-amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, our primary goal is to underscore the progress made in the development of next-generation sequencing. This progress aims to enhance our understanding of the disease mechanisms and explore gene-based therapies for NDDs. Throughout this review, we focus on genetic variations, methodologies for their identification, the associated pathophysiology, and the promising potential of gene therapy. Ultimately, our objective is to provide a comprehensive and forward-looking perspective on the emerging research arena of NDDs.},
}

Humans
*Neurodegenerative Diseases/genetics/therapy/pathology
*Parkinson Disease/genetics/therapy/pathology
*Alzheimer Disease/pathology
*Amyotrophic Lateral Sclerosis/genetics

@article {pmid38396946,
year = {2024},
author = {Anilkumar, AK and Vij, P and Lopez, S and Leslie, SM and Doxtater, K and Khan, MM and Yallapu, MM and Chauhan, SC and Maestre, GE and Tripathi, MK},
title = {Long Non-Coding RNAs: New Insights in Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {4},
pages = {},
pmid = {38396946},
issn = {1422-0067},
support = {R16 GM146696/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics/pathology ; *RNA, Long Noncoding/genetics ; *Alzheimer Disease ; *Parkinson Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are gradually becoming a burden to society. The adverse effects and mortality/morbidity rates associated with these NDDs are a cause of many healthcare concerns. The pathologic alterations of NDDs are related to mitochondrial dysfunction, oxidative stress, and inflammation, which further stimulate the progression of NDDs. Recently, long non-coding RNAs (lncRNAs) have attracted ample attention as critical mediators in the pathology of NDDs. However, there is a significant gap in understanding the biological function, molecular mechanisms, and potential importance of lncRNAs in NDDs. This review documents the current research on lncRNAs and their implications in NDDs. We further summarize the potential implication of lncRNAs to serve as novel therapeutic targets and biomarkers for patients with NDDs.},
}

Humans
*Neurodegenerative Diseases/genetics/pathology
*RNA, Long Noncoding/genetics
*Alzheimer Disease
*Parkinson Disease/genetics
*Amyotrophic Lateral Sclerosis/genetics

@article {pmid38393299,
year = {2024},
author = {García-Parra, B and Guiu, JM and Povedano, M and Mariño, EL and Modamio, P},
title = {Geographical distribution of clinical trials in amyotrophic lateral sclerosis: a scoping review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {25},
number = {3-4},
pages = {376-381},
doi = {10.1080/21678421.2024.2320881},
pmid = {38393299},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics/therapy ; Belgium ; France ; Germany ; United Kingdom ; },
abstract = {Introduction: Clinical trials location is determined by many factors, including the availability of patient populations, regulatory environment, scientific expertise, and cost considerations. In clinical drug development of amyotrophic lateral sclerosis (ALS), where genetic differences have been described and may be related to geographic setting, this could have implications for the clinical interpretation of results in underrepresented geographic settings. Objective: The aim of this study was to review country participation in ALS clinical research based on available data from clinical trial registries and databases. Methods: We performed a scoping review with available information about clinical trials on ALS in ClinicalTrials.gov (CT), EU clinical trials register (EudraCT), WHO International Clinical Trials Registry Platform (ICTRP) and Web of Science (WOS). Inclusion criteria were clinical trials in phase 2 and 3 to treat ALS, recruiting or active not recruiting, from 23/06/2018 to 23/06/2023. Results: The total number of clinical trials identified were 188; 54 studies in CT, 38 in EudraCT, 47 in ICTRP and 49 in WOS. We identified 77 clinical trials after deleting duplicates and applying exclusion criteria. The countries with most studies conducted were the US with 35 studies (10.9%), followed by the United Kingdom, Belgium, France and Germany with 21 studies each one of them (6.5%). Conclusion: The data obtained in our review showed a non-homogeneous distribution in clinical trials at the international level, which may influence the interpretation of the results obtained.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/genetics/therapy
Belgium
France
Germany
United Kingdom

@article {pmid38392286,
year = {2024},
author = {Jackson, WS and Bauer, S and Kaczmarczyk, L and Magadi, SS},
title = {Selective Vulnerability to Neurodegenerative Disease: Insights from Cell Type-Specific Translatome Studies.},
journal = {Biology},
volume = {13},
number = {2},
pages = {},
pmid = {38392286},
issn = {2079-7737},
support = {grant # 990868//the Konung Gustaf V:s och Drottning Victorias Stiftelse; the Wallenberg Center for Molecular Medicine;the Hereditary Disease Foundation/ ; },
abstract = {Neurodegenerative diseases (NDs) manifest a wide variety of clinical symptoms depending on the affected brain regions. Gaining insights into why certain regions are resistant while others are susceptible is vital for advancing therapeutic strategies. While gene expression changes offer clues about disease responses across brain regions, the mixture of cell types therein obscures experimental results. In recent years, methods that analyze the transcriptomes of individual cells (e.g., single-cell RNA sequencing or scRNAseq) have been widely used and have provided invaluable insights into specific cell types. Concurrently, transgene-based techniques that dissect cell type-specific translatomes (CSTs) in model systems, like RiboTag and bacTRAP, offer unique advantages but have received less attention. This review juxtaposes the merits and drawbacks of both methodologies, focusing on the use of CSTs in understanding conditions like amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), and specific prion diseases like fatal familial insomnia (FFI), genetic Creutzfeldt-Jakob disease (gCJD), and acquired prion disease. We conclude by discussing the emerging trends observed across multiple diseases and emerging methods.},
}

@article {pmid38391754,
year = {2024},
author = {Leão Batista Simões, J and Webler Eichler, S and Raitz Siqueira, ML and de Carvalho Braga, G and Bagatini, MD},
title = {Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.},
journal = {Brain sciences},
volume = {14},
number = {2},
pages = {},
pmid = {38391754},
issn = {2076-3425},
support = {Proj. No 404256/2021-0 and 310606/2021-7).//National Council for Scientific and Technological Development/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.},
}