@article {pmid41510716,
year = {2026},
author = {Bano, A and Khan, AA and Kushwaha, SP and Aleena, and Zaidi, SMH and Misbahul Hasan, S and Fatima, A},
title = {Indole Scaffolds in Neurological Therapeutics: Synthesis, Structure- Activity Relationships and Drug-Receptor Interactions.},
journal = {Mini reviews in medicinal chemistry},
volume = {26},
number = {13},
pages = {1046-1069},
pmid = {41510716},
issn = {1875-5607},
mesh = {Humans ; *Indoles/chemistry/chemical synthesis/pharmacology/therapeutic use ; Structure-Activity Relationship ; *Nervous System Diseases/drug therapy ; Animals ; *Neuroprotective Agents/chemical synthesis/chemistry/pharmacology/therapeutic use ; Molecular Structure ; },
abstract = {INTRODUCTION: Indole is a privileged heterocyclic scaffold that plays a crucial role in medicinal chemistry due to its strong ability to bind to various biological receptors and interact with diverse molecular targets. Indole exhibits both biological and chemical significance. Its structural versatility allows for precise chemical modifications, making it an essential framework in drug discovery. This review discusses the structure-activity relationships, synthesis, and interactions of indole derivatives, particularly in relation to targets within the central nervous system.

METHODS: A detailed literature survey was conducted using databases such as Google Scholar, Elsevier, PubMed, ACS, PubChem, ScienceDirect, and RSC to understand the structural modifications of indole derivatives and their therapeutic potential. Both research and review articles related to indole- based compounds were thoroughly studied to prepare this review article.

RESULTS: There are over 40 FDA-approved drugs containing an indole nucleus used to treat various diseases, underscoring its potential in neurotherapeutics. This review highlights innovative synthetic strategies, including green chemistry approaches, that improve the drug-likeness and bioavailability of indole derivatives. Indole continues to be an indispensable scaffold in the development of novel therapeutics aimed at addressing the growing burden of neurological disorders.

DISCUSSION: This review aims to provide a comprehensive analysis of the therapeutic potential of indole-based compounds for the treatment of neurological disorders. However, challenges like blood-brain barrier permeability and long-term safety must be addressed for clinical success. Nonetheless, this review will help in designing and developing newer indole-based molecules in the discovery of neurological drug development.

CONCLUSION: Due to its broad spectrum of biological activities and favorable pharmacokinetic properties, indole is an impressive scaffold for the treatment of various neurological disorders. Indole demonstrates remarkable therapeutic potential against a range of central nervous system-related conditions, including Alzheimer's disease, epilepsy, migraine, stroke, Parkinson's disease, prion disease, amyotrophic lateral sclerosis, and Huntington's disease.},
}

Humans
*Indoles/chemistry/chemical synthesis/pharmacology/therapeutic use
Structure-Activity Relationship
*Nervous System Diseases/drug therapy
Animals
*Neuroprotective Agents/chemical synthesis/chemistry/pharmacology/therapeutic use
Molecular Structure

@article {pmid41588889,
year = {2026},
author = {Thakur, A and Chowdhury, KR and Kumar, A and Sharma, VV and Bhatia, R},
title = {Targeting Non-coding RNAs in Neurodegeneration: Advances in Therapeutic RNA Modalities and Next-Gen Delivery Technologies.},
journal = {Current Alzheimer research},
volume = {23},
number = {4},
pages = {245-269},
pmid = {41588889},
issn = {1875-5828},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/genetics ; *RNA, Untranslated/therapeutic use/genetics ; Animals ; MicroRNAs ; *Genetic Therapy/methods ; Drug Delivery Systems ; },
abstract = {Non-coding RNA (ncRNA)-based therapies represent an emerging and transformative approach in the treatment of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)/Motor Neuron Disease (MND). This review explored the potential for targeting microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, reinforced by promising results from clinical trials demonstrating their capacity to modulate disease pathways. The incorporation of cutting-edge computational methodologies, including RNA structure prediction and gene regulatory network analysis, has been at the forefront in enhancing the efficacy of ncRNA-based treatments. Moreover, chemical methods have improved RNA molecules' stability, accuracy, and directed delivery, enhancing their therapeutic effects. Moreover, cutting-edge RNA editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats/CRISPRassociated protein 13 (CRISPR/Cas13) are advancing our ability to directly manipulate ncRNA expression, offering a powerful avenue for addressing the molecular origins of neurodegeneration. Despite these advances, challenges persist, particularly in ensuring the specificity, delivery efficiency, and long-term efficacy of these treatments. Nanotechnology provides innovative solutions to these obstacles, facilitating more efficient and precise RNA delivery, especially to neuronal tissue. In conclusion, ncRNA-based therapies, while still in nascent stages, represent a hopeful frontier in the fight against NDs. With ongoing research and technological advancements, these therapies could not only halt disease progression but also redefine the future of ND treatment, offering new avenues for patients' care and clinical success.},
}

Humans
*Neurodegenerative Diseases/therapy/genetics
*RNA, Untranslated/therapeutic use/genetics
Animals
MicroRNAs
*Genetic Therapy/methods
Drug Delivery Systems

@article {pmid42526365,
year = {2026},
author = {Ahsan, A and Ou, JC and Majumder, P and Chiang, YH and Huang, JK and Huang, CS},
title = {A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.},
journal = {Journal of neuroimmunology},
volume = {420},
number = {},
pages = {579028},
doi = {10.1016/j.jneuroim.2026.579028},
pmid = {42526365},
issn = {1872-8421},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/complications ; *Tomography, Optical Coherence/methods ; *Retina/diagnostic imaging/pathology ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS.

METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I[2] statistic.

RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant.

CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder.

PROSPERO identifier CRD420251076035.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/complications
*Tomography, Optical Coherence/methods
*Retina/diagnostic imaging/pathology

@article {pmid42580558,
year = {2026},
author = {Armoundas, AA and Piperi, C},
title = {Epigenetic drift and LINE-1 activation in aging brain: Implications for neurodegenerative disease.},
journal = {Mechanisms of ageing and development},
volume = {233},
number = {},
pages = {112235},
doi = {10.1016/j.mad.2026.112235},
pmid = {42580558},
issn = {1872-6216},
mesh = {Humans ; *Long Interspersed Nucleotide Elements ; *Epigenesis, Genetic ; *Aging/genetics/metabolism/pathology ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *Brain/metabolism/pathology ; *DNA Methylation ; Animals ; },
abstract = {Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.},
}

Humans
*Long Interspersed Nucleotide Elements
*Epigenesis, Genetic
*Aging/genetics/metabolism/pathology
*Neurodegenerative Diseases/genetics/metabolism/pathology
*Brain/metabolism/pathology
*DNA Methylation
Animals

@article {pmid42694478,
year = {2026},
author = {Cui, Q and Zheng, K and Liu, Q and Wang, L and Liu, Y and Bai, R and Zhang, W and Guo, J and Chang, X and Wang, J},
title = {From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1921079},
pmid = {42694478},
issn = {1662-5099},
abstract = {Microglia are brain-resident myeloid cells that maintain central nervous system homeostasis and respond dynamically to neuronal injury, protein aggregation, and alterations in the local metabolic environment. Single-cell and single-nucleus studies demonstrate that microglial responses in neurodegenerative diseases are highly heterogeneous and cannot be adequately explained by the classical M1/M2 polarization model. Increasing evidence further indicates that metabolic remodeling is not merely a consequence of activation but a determinant of microglial migration, phagocytosis, inflammatory signaling, redox balance, organelle function, and interactions with surrounding neural cells. In this review, we propose a microglial immunometabolic trajectory framework in which metabolic states are viewed as branching and potentially reversible determinants of cellular function rather than fixed stages of a universal disease pathway. We summarize how glucose metabolism, mitochondrial function, lipid metabolism, amino acid metabolism, lysosomal activity, and redox regulation shape microglial plasticity. We further examine relationships among transcriptionally defined states, including disease-associated microglia, microglia associated with neurodegeneration, lipid-droplet-accumulating microglia, and other disease-enriched populations, while emphasizing that transcriptional similarity does not necessarily imply metabolic function or lineage progression. Comparative evidence from Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis indicates that common metabolic regulators, including HIF-1α, mTOR, PKM2, TREM2, APOE, and NLRP3, exert disease-specific effects with unequal mechanistic support. We further distinguish associative metabolic signatures from intervention-based causal evidence and discuss limitations of animal models, immortalized cell lines, postmortem tissue, and induced pluripotent stem cell-derived microglia. Finally, we highlight the need for cell-specific, state-resolved, and temporally precise metabolic interventions that restore defined microglial functions without compromising physiological immune surveillance.},
}

@article {pmid42694654,
year = {2026},
author = {Wu, Y and Duan, L and Zhang, L and Wang, S and Yan, H and He, M and Wang, T and Li, L and Gao, Y},
title = {TREM2 as a central hub of neuroimmune-metabolic crosstalk in central nervous system disorders: from microglial biology to therapeutic targeting.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1912989},
pmid = {42694654},
issn = {1664-3224},
mesh = {Humans ; *Microglia/metabolism/immunology ; *Receptors, Immunologic/metabolism/genetics/immunology ; *Membrane Glycoproteins/metabolism/genetics/immunology ; Animals ; *Central Nervous System Diseases/metabolism/immunology/therapy ; Signal Transduction ; *Neuroimmunomodulation ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-enriched immunoreceptor that functions as a central regulator of microglial adaptation by integrating immune surveillance, lipid sensing, metabolic reprogramming, and phagocytic responses in the central nervous system (CNS). Through association with the adaptor protein DAP12, TREM2 activates interconnected signaling networks involving the SYK pathway, PLCγ2-mediated Ca[2+] signaling, PI3K-AKT-mTOR signaling, NF-κB activation and inflammatory regulatory pathways, thereby shaping microglial survival, migration, clearance capacity, and interactions with surrounding neural and immune cells. Increasing evidence from genetic studies, single-cell transcriptomics, spatial analyses, and human-derived microglial models indicates that TREM2 dysfunction contributes to diverse CNS disorders; however, its biological consequences are highly dependent on disease stage, pathological substrate, cellular context, and microenvironmental cues. In Alzheimer's disease, TREM2 regulates amyloid-β-associated microglial responses, lipid metabolism, and synaptic remodeling, while its effects on tau-driven neurodegeneration remain controversial. In Parkinson's disease, stroke, epilepsy, and amyotrophic lateral sclerosis, TREM2 influences α-Syn clearance, inflammatory resolution, tissue repair, and microglial state transitions, but may exert beneficial or maladaptive effects depending on temporal dynamics and disease-specific stressors. Emerging clinical evidence, including TREM2 variants, soluble TREM2 (sTREM2) biomarkers, and human multi-omics studies, highlights both the translational potential and complexity of targeting this pathway. Herein, this review summarizes the molecular mechanisms, physiological functions, and disease-specific roles of TREM2 in CNS disorders, critically discusses unresolved controversies and species-specific challenges, and evaluates emerging therapeutic strategies toward biomarker-guided and stage-specific modulation of TREM2 signaling. Understanding how to restore appropriate microglial adaptability rather than simply enhance or suppress TREM2 activity may provide a foundation for precision therapies in CNS disorders.},
}

Humans
*Microglia/metabolism/immunology
*Receptors, Immunologic/metabolism/genetics/immunology
*Membrane Glycoproteins/metabolism/genetics/immunology
Animals
*Central Nervous System Diseases/metabolism/immunology/therapy
Signal Transduction
*Neuroimmunomodulation

@article {pmid42697379,
year = {2026},
author = {Mohammad, SI and Vasudevan, A and Oriquat, G and Gajjar, TB and Hanumanthayya, M and Shukla, SK and Tailor, NK and Baig, MR and Fadaam, O and Abdul, AS},
title = {Extracellular Vesicles in Neurodegenerative Diseases: A New Frontier in Diagnosis and Therapy.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116455},
doi = {10.1016/j.bbr.2026.116455},
pmid = {42697379},
issn = {1872-7549},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the progressive disorders of the nervous system that are characterized by the gradual destruction of neurons, the accumulation of misfolded proteins, and the limited effective therapeutic options. In recent years, numerous lines of evidence have emphasized the important role of extracellular vesicles (EVs) in the formation and progression of these diseases. These vesicles are membrane-bound nanoscale structures that are secreted by almost all cell types and play a role in cell-cell communication through the transfer of molecules such as proteins, lipids, and nucleic acids. In neurodegenerative disorders, EVs can facilitate the transport and dissemination of disease-related proteins, including amyloid-β, tau, α-synuclein, mutant huntingtin, SOD1, and TDP-43, thus contributing to the spread of pathological processes in different parts of the nervous system. On the other hand, the ability of these vesicles to cross the blood-brain barrier and reflect molecular changes occurring in the central nervous system makes them valuable candidates for the development of minimally invasive biomarkers. This review reviews the biogenesis, classification, isolation methods, and molecular content of EVs, and analyzes their role in the pathogenesis, diagnosis, and treatment of the most important neurodegenerative diseases. Also, the importance of EV-associated proteins, RNAs, and lipids as emerging diagnostic biomarkers, as well as the therapeutic potential of natural and engineered vesicles as drug delivery systems and regulators of neuroinflammation and neurodegenerative processes, is discussed.},
}

@article {pmid41416937,
year = {2026},
author = {Jensen, TR and Jacobs, I and Kverková, K and Lalić, L and Polonyiová, A and Stehlík, P and Reber, SA and Osvath, M},
title = {T. rex cognition was T. rex-like-A critical outlook on diverging views of the neurocognitive evolution in dinosaurs.},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {309},
number = {10},
pages = {2541-2559},
doi = {10.1002/ar.70074},
pmid = {41416937},
issn = {1932-8494},
mesh = {Animals ; *Dinosaurs/physiology/anatomy & histology ; *Cognition/physiology ; *Biological Evolution ; *Brain/physiology/cytology ; Neurons/physiology/cytology ; },
abstract = {A recent debate has emerged between Caspar et al. (2024) and Herculano-Houzel (2023) on inferring extinct dinosaur cognition by estimating brain neuron counts. While thought-provoking, the discussion largely overlooks the function of cognition, as well as partly neglects the difficulties involved in estimating neuron numbers, which according to us leads to oversimplified conclusions. We use this exchange as a springboard to further explore how extinct cognition might be studied and the potential pitfalls involved. One of the main emphases is on introducing basic concepts and contemporary views of cognition and its evolution. In relation to this, we highlight the shift in thermobiology during the Mesozoic-from ectothermy to endothermy-and its major impact on cognition and brain evolution. We also examine the challenges of estimating neuron counts in extinct dinosaurs based on current knowledge and take issue with several aspects of the approaches used by both Caspar et al. and Herculano-Houzel. At the same time, we challenge Caspar et al.'s claim that telencephalic neuron numbers, if estimable, would be largely uninformative about extinct dinosaur cognition, while also disagreeing with Herculano-Houzel's somewhat reductive view. We further emphasize the value of comparative cognitive studies in extant animals, alongside neural correlates, to infer the cognitive evolution of non-avian dinosaurs. We briefly outline how cognition is studied in living species and the extent to which such research can inform evolutionary inference. Our focus here is on non-avian theropods, as they are central to the current debate and belong to the lineage that led to modern birds.},
}

Animals
*Dinosaurs/physiology/anatomy & histology
*Cognition/physiology
*Biological Evolution
*Brain/physiology/cytology
Neurons/physiology/cytology

@article {pmid42694267,
year = {2026},
author = {Heffernan, ÁB and Do, F and Carter, E and Al-Tameemi, F and Selvaraj, BT and Stavrou, M},
title = {Disrupted astrocyte-neuron metabolic coupling in amyotrophic lateral sclerosis.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1899307},
pmid = {42694267},
issn = {2296-634X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by progressive loss of motor neurons. In addition to neurodegeneration, ALS is increasingly recognised as a disorder associated with widespread metabolic dysfunction, including hypermetabolism, weight loss, and dyslipidaemia, all of which correlate with disease progression and survival. Astrocytes play a central role in maintaining metabolic homeostasis in the central nervous system by supporting neuronal energy demands, regulating glutamate levels, buffering oxidative stress, and maintaining lipid balance. Emerging evidence suggests that disruption of these supportive astrocytic functions may contribute directly to motor neuron vulnerability in ALS. In this mini-review, we discuss how alterations in astrocyte metabolism may impair astrocyte-neuron metabolic coupling in ALS. We summarise work from human studies and experimental models demonstrating abnormalities in astrocytic glycolysis, mitochondrial function, lactate shuttling, lipid metabolism, and glutamate homeostasis. We highlight growing evidence implicating mitochondrial dysfunction and impaired lipid handling in astrocytes as important contributors to disease progression. We explore how these changes may deprive motor neurons of metabolic and antioxidant support while also promoting excitotoxicity, oxidative stress, and lipotoxicity. We also discuss how recent advances in human induced pluripotent stem cell models, metabolomics, and single-cell transcriptomics are improving our understanding of astrocyte dysfunction in ALS. Finally, we consider current and emerging therapeutic strategies aimed at restoring astrocytic metabolic function. Together, these findings support the idea that progressive failure of astrocyte-mediated metabolic support is an important component of ALS pathogenesis and may represent a promising therapeutic target.},
}

@article {pmid42693185,
year = {2026},
author = {Dalakas, MC and Lünemann, JD},
title = {Role of complement and complement-targeted therapeutics in neurological diseases.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42693185},
issn = {1759-4766},
abstract = {Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains primarily focused on diseases with complement-fixing pathogenic antibodies (such as myasthenia gravis and neuromyelitis optica spectrum disorder), a robust pipeline of emerging treatments holds promise for expanding complement-targeted therapies to a broader spectrum of autoimmune neurological diseases, such as multiple sclerosis and even neurodegenerative diseases such as Alzheimer disease or amyotrophic lateral sclerosis. This Review presents insights into complement biology as it relates to the development or initiation of autoimmune and possibly degenerative diseases affecting the central and peripheral nervous systems or muscle. The effects, merits, risks and challenges of marketed drugs or biologic agents in ongoing phase I-III clinical trials engineered to inhibit proximal or distal components of the complement cascade are also discussed. Anti-complement therapeutics are destined to change the treatment of autoimmune neurologic conditions in which the therapeutic landscape is now becoming crowded with biologic agents targeting other key autoimmunity factors.},
}

@article {pmid42689185,
year = {2026},
author = {Sun, L and Yu, X and Yin, H and Bi, J and Lou, H and Pei, H},
title = {A recent review on ginseng's effects on neurodegenerative diseases: active ingredients, mechanisms of action, applications, and delivery strategies.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1912520},
pmid = {42689185},
issn = {2296-861X},
abstract = {BACKGROUND: Neurodegenerative diseases (NDDs) pose a major health challenge due to their high prevalence and the lack of effective treatments; ginseng, as medicine and food homology, has potential neuroprotective effects.

METHODS: This article provides a systematic review of research conducted over the past five years on the use of ginseng to treat NDDs, summarizing and analyzing the findings in four key areas: active components, mechanisms of action, clinical applications, and novel delivery strategies.

RESULTS: Ginsenosides are the core active ingredients in ginseng, while polysaccharides, essential oils, and peptides also exert synergistic effects through various pathways; their mechanisms of action include regulating Aβ/tau protein aggregation, inhibiting microglial activation, reducing glutamate excitotoxicity, and restoring mitochondrial function and antioxidant balance. In models of AD, PD, HD, and ALS, ginseng's active components have been shown to improve both behavioral and pathological indicators, while novel delivery strategies (nanoparticles, exosomes, and engineered cellular carriers) can significantly enhance blood-brain barrier permeability and brain-targeting efficiency.

CONCLUSION: Ginseng exhibits protective effects against NDDs through multiple mechanisms of action. However, current evidence is largely limited to preclinical studies, and future efforts should focus on advancing the clinical translation of safe and effective brain-targeted delivery systems.},
}

@article {pmid42677779,
year = {2026},
author = {Ali, A and Arif, M and Ashraf, U and Elahi, S and Mustafa, A and Yasir, MB and Sarfraz, W and Ansari, AU and Masood, HMY and Shabbir, MA and Abdullah, A and Sharma, MK},
title = {CSF Tau and Amyloid Biomarkers in Cognitive Impairment Across the ALS-FTD Spectrum: A Systematic Narrative Review and Evidence Map.},
journal = {Brain and behavior},
volume = {16},
number = {9},
pages = {e71740},
pmid = {42677779},
issn = {2162-3279},
mesh = {Humans ; *tau Proteins/cerebrospinal fluid ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/complications ; Biomarkers/cerebrospinal fluid ; *Frontotemporal Dementia/cerebrospinal fluid/complications ; *Amyloid beta-Peptides/cerebrospinal fluid ; *Cognitive Dysfunction/cerebrospinal fluid/etiology ; },
abstract = {INTRODUCTION: Cognitive impairment is an important non-motor manifestation of amyotrophic lateral sclerosis (ALS), particularly across the ALS-frontotemporal dementia (ALS-FTD) spectrum. Cerebrospinal fluid (CSF) tau and amyloid biomarkers may reflect nonspecific neurodegenerative injury, concomitant Alzheimer disease (AD) pathology, or distinct cognitive phenotypes. However, available evidence remains limited, fragmented, and methodologically heterogeneous.

METHODS: This systematic narrative review and semi-quantitative evidence map was conducted according to PRISMA 2020 recommendations. PubMed, Scopus, Web of Science, and Google Scholar were searched from database inception through May 2026. Eligible observational studies reported cognition-specific associations between CSF tau, amyloid, or related neurodegenerative biomarkers and cognitive outcomes in ALS-spectrum populations. Two reviewers independently screened studies, extracted quantitative effect estimates, and assessed risk of bias using the Newcastle-Ottawa Scale. Cross-study consistency was summarized using an exploratory semi-quantitative evidence-coding framework.

RESULTS: Four observational studies comprising 638 ALS-spectrum participants fulfilled the eligibility criteria. Total tau and p-tau181 showed the most reproducible associations with cognition. Total tau correlated with ECAS total (r = -0.398, P < 0.001) and ALS-specific cognition (r = -0.403, P < 0.001), while adjusted multicenter analyses demonstrated associations between p-tau181 and ECAS total (β = -0.03, p = 0.006) and memory performance (β = -0.04, p = 0.003). Both biomarkers received ++ evidence-map coding. Amyloid findings were more heterogeneous; lower Aβ42/Aβ40 was associated with poorer memory performance (β = 0.20, p = 0.044), but continuous amyloid-cognition associations were not consistently replicated across cohorts (± evidence). Broader CSF protein-ratio findings remained exploratory. Clinical, cognitive, assay, and analytical heterogeneity precluded meta-analysis.

CONCLUSIONS: The available evidence, although limited and heterogeneous, suggests that total tau may primarily reflect broader neurodegenerative injury, whereas p-tau181 and Aβ42/Aβ40 may be more informative for selected cognitive phenotypes or possible AD co-pathology. These biomarkers should remain research tools until larger, standardized, longitudinal multicenter studies establish their pathological specificity, predictive value, and clinical utility.},
}

Humans
*tau Proteins/cerebrospinal fluid
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/complications
Biomarkers/cerebrospinal fluid
*Frontotemporal Dementia/cerebrospinal fluid/complications
*Amyloid beta-Peptides/cerebrospinal fluid
*Cognitive Dysfunction/cerebrospinal fluid/etiology

@article {pmid42677831,
year = {2026},
author = {Basak, B and Riley, JF and Nataraj, NM and Holzbaur, EL},
title = {Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {17},
pages = {},
pmid = {42677831},
issn = {1558-8238},
mesh = {Humans ; *Mitophagy ; Animals ; *Neurons/pathology/metabolism ; *Mitochondria/pathology/metabolism/genetics ; PTEN-Induced Putative Kinase ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Protein Kinases/metabolism/genetics ; Ubiquitin-Protein Ligases/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Signal Transduction ; },
abstract = {Regulation of mitochondrial health is critical for maintaining cellular homeostasis in the nervous system. Damaged mitochondria can have detrimental effects on neuronal health and are thought to be key contributors to the progression of neurodegenerative disorders including Parkinson's disease and amyotrophic lateral sclerosis. To mitigate this damage, multiple quality control mechanisms have evolved to eliminate aged or damaged mitochondria. One such quality control process is autophagy, a process that involves turnover of mitochondria at presynaptic sites and the axon terminal under basal conditions. This highly conserved mechanism sequesters mitochondria from the cytosol within autophagosomes followed by degradation upon fusion with a lysosome. Acute mitochondrial damage activates a selective form of autophagy called mitophagy that involves receptor-mediated engulfment and degradation of the damaged organelle. Multiple mechanisms have been shown to drive efficient mitophagy in neurons and glia, including PTEN induced kinase 1 (PINK1)/Parkin-dependent mitophagy and receptor-mediated mitophagy. Genetic, pathological, and experimental evidence all implicate defects in the removal of damaged mitochondria in the onset or progression of neurodegenerative disease. Both the initiation of PINK1/Parkin-dependent mitophagy and deficits in the removal of damaged mitochondria are linked to activation of neuroinflammatory pathways, including NF-κB and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. In this Review, we discuss the molecular pathways governing mitophagy in neurons and glial cells and how deficits in these pathways may lead to neurodegeneration. We also highlight emerging therapeutic strategies aimed at restoring mitophagy to preserve neuronal homeostasis and function.},
}

Humans
*Mitophagy
Animals
*Neurons/pathology/metabolism
*Mitochondria/pathology/metabolism/genetics
PTEN-Induced Putative Kinase
*Neurodegenerative Diseases/metabolism/pathology/genetics
Protein Kinases/metabolism/genetics
Ubiquitin-Protein Ligases/metabolism/genetics
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
Signal Transduction

@article {pmid42681667,
year = {2026},
author = {Sowoidnich, L and Norman, AL and Gerstner, F and Siemund, JK and Buettner, JM and Pagiazitis, JG and Dreilich, V and Pilz, K and Tian, D and Sumner, CJ and Paradis, A and Mentis, GZ and Simon, CM},
title = {A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42681667},
issn = {2051-5960},
mesh = {Animals ; Humans ; *Motor Neurons/pathology ; *Neurodegenerative Diseases/pathology ; *Spinal Cord/pathology ; Muscular Atrophy, Spinal/pathology ; Mice ; Disease Models, Animal ; },
abstract = {Motor neuron (MN) loss is a hallmark of neurodegenerative disorders, yet its assessment remains variable, confounding mechanistic and therapeutic interpretation. To address this, we conducted a systematic review and meta-analysis of spinal muscular atrophy (SMA) mouse studies, revealing 60% variability in reported MN loss, for which spinal cord sampling emerged as a major contributor. Using a whole-segment approach with tissue clearing, MN tracing, and multimodal imaging, we confirmed segment-dependent differences in MN counts. Common MN markers (SMI-32, Nissl) lacked specificity, whereas choline acetyltransferase (ChAT) provided robust labeling in murine and human spinal cords. Deep learning-based whole-mount segmentation enabled unbiased MN quantification and validated manual counts. Integrating analysis with computational modeling established segment sampling as a key driver of variability and revealed degeneration patterns: widespread MN loss in amyotrophic lateral sclerosis (ALS), selective MN loss in severe SMA, and preservation in mild SMA models. These findings establish a framework for reproducible MN quantification.},
}

Animals
Humans
*Motor Neurons/pathology
*Neurodegenerative Diseases/pathology
*Spinal Cord/pathology
Muscular Atrophy, Spinal/pathology
Mice
Disease Models, Animal

@article {pmid42684942,
year = {2026},
author = {Huang, D and Zhang, Z and Gong, X},
title = {Context-dependent roles of osteopontin in aging-related neurological disorders.},
journal = {The Journal of international medical research},
volume = {54},
number = {9},
pages = {3000605261476190},
pmid = {42684942},
issn = {1473-2300},
mesh = {Humans ; *Osteopontin/metabolism ; *Aging/pathology/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Brain/pathology/metabolism ; Alzheimer Disease ; Microglia/metabolism ; },
abstract = {Osteopontin (encoded by secreted phosphoprotein 1) is a multifunctional matricellular phosphoglycoprotein that has emerged as an important mediator in the aging nervous system. During aging, osteopontin interacts with microglial priming, vascular remodeling, myelin repair, and innate immune responses and is consistently implicated in major late-life neurological disorders. However, its biological effects are highly context dependent. Depending on its cellular source, proteolytic processing, receptor interactions, anatomical distribution, and disease stage, osteopontin may either exacerbate chronic neuroinflammation and tissue injury or promote phagocytic clearance, neuronal survival, remyelination, neuroplasticity, and tissue repair. This review critically synthesizes studies indexed in PubMed and Google Scholar through 3 April 2026 on the role of osteopontin in brain aging, Alzheimer's disease and related dementias, Parkinson's disease and Lewy body disorders, cerebrovascular disease, vascular cognitive impairment, cerebral small vessel disease, and amyotrophic lateral sclerosis. In Alzheimer's disease, cerebrospinal fluid and plasma osteopontin concentrations increase from the prodromal to symptomatic stages, whereas microglial or perivascular secreted phosphoprotein 1 expression correlates with amyloid pathology, synaptic remodeling, and cognitive decline. However, under specific conditions, osteopontin also enhances macrophage-mediated amyloid-beta clearance. In stroke, elevated circulating osteopontin predicts poor clinical outcomes, whereas experimental studies demonstrate that appropriately timed exogenous osteopontin, regulatory T cell-derived osteopontin, and osteopontin-mediated autophagic and reparative pathways promote white-matter repair, peri-infarct plasticity, and blood-brain barrier integrity. Evidence from Parkinson's disease, Lewy body disease, frontotemporal dementia, and amyotrophic lateral sclerosis further supports the role of osteopontin as both a candidate biomarker and a regulator of selective neuronal vulnerability. Rather than being uniformly detrimental or protective, osteopontin should be regarded as a context-dependent regulator of age-related neuroimmune remodeling. This perspective reconciles seemingly conflicting findings and supports the development of therapeutic strategies that are tailored to disease stage, protein fragment, and cell type rather than broadly targeting osteopontin.},
}

Humans
*Osteopontin/metabolism
*Aging/pathology/metabolism
Animals
*Nervous System Diseases/metabolism/pathology
Brain/pathology/metabolism
Alzheimer Disease
Microglia/metabolism

@article {pmid42685299,
year = {2026},
author = {Benatar, M and Rothstein, JD and Snow, K and Sethi, N and Taylor, DM and Dave, KD and McDermott, CJ and Cochrane, TI},
title = {Repairing the Amyotrophic Lateral Sclerosis Trial Credibility Gap.},
journal = {Neurology},
volume = {107},
number = {7},
pages = {e218471},
doi = {10.1212/WNL.0000000000218471},
pmid = {42685299},
issn = {1526-632X},
mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Clinical Trials as Topic/standards ; *Research Design/standards ; },
abstract = {There is a long history of early- and mid-phase amyotrophic lateral sclerosis (ALS) clinical trial data being used to make claims of clinical benefit that fail to translate into successful phase 3 outcomes. It is suggested that fallacious scientific reasoning is being encouraged by perverse incentives arising from a "clinical trial industrial complex" that greatly influences trial design, data interpretation, and results communication. Recurring fallacies include false premises underlying outcome comparisons, misuse and incorrect interpretation of biomarkers, mismatches between study design and stated objectives, selective reporting of outcomes, over-reliance on post hoc analyses and open-label extension data, and overly optimistic framing of inconclusive data. We argue that these practices, reinforced by misaligned incentives across industry and academia, lead to premature claims of therapeutic promise and tangible harm to patients. To address the resulting ALS clinical trial credibility gap, we call for rigorous adherence to established standards for reporting clinical trial results, clearer distinction between hypothesis generation and hypothesis testing, more measured description of trial results, and more disciplined triage of phase 2 programs. A cultural shift toward scientific skepticism and methodological rigor is essential to accelerate the development of genuinely effective ALS therapies.},
}

*Amyotrophic Lateral Sclerosis/therapy
Humans
*Clinical Trials as Topic/standards
*Research Design/standards

@article {pmid42686219,
year = {2026},
author = {Liu, J and Lin, J and Liu, H and Soh, K and Ju, Q and Soh, K and Dong, X},
title = {Efficacy of Antimicrobial Lock Solutions on Central Line-Associated Bloodstream Infection and Catheter Survival in Hemodialysis Patients: A Systematic Review and Meta-Analysis.},
journal = {Seminars in dialysis},
volume = {},
number = {},
pages = {},
doi = {10.1111/sdi.70046},
pmid = {42686219},
issn = {1525-139X},
support = {202301A014//Chengde Science and Technology Program/ ; GJXH2021-126//Hebei Higher Education Association "14th Five-Year Plan" Research Project/ ; H2026406068//Hebei Natural Science Foundation/ ; 202307//Chengde Medical university Project/ ; 202404//Chengde Medical university Project/ ; },
abstract = {Hemodialysis (HD) catheters carry a high risk of life-threatening bloodstream infections and failure. Antimicrobial lock solutions (ALS) are used to reduce this risk, but their overall efficacy on key outcomes like infection rates and catheter survival requires comprehensive evaluation. This systematic review and meta-analysis assess the impact of ALS on preventing catheter-related bloodstream infections (including incidence and density) and on improving catheter survival. A systematic search was conducted across the databases of PubMed, Embase, Scopus, Cochrane Library, and Google Scholar. A meta-analysis was conducted using STATA software. A total of 1183 studies were screened based on title and abstract, and further 282 studies were evaluated in full text. Eventually, 14 studies with 15 treatment arms were included. Key outcomes including central line-associated bloodstream infection (CLABSI), exit infection, and catheter-free survival were conducted separately. ALS demonstrated statistically significant benefits on CLABSI infection and catheter-free survival compared to nonantimicrobial solutions, showing a reduction in CLABSI density with a pooled log odd ratio (logOR) of -1.29 (95% CI: -1.59 to -0.99), lower CLABSI rates (pooled logOR = -1.50, 95% CI: -1.85 to -1.15), and improved catheter-free survival with log hazard ratio (logHR) of -1.11 (95% CI: -1.41 to -0.8). Consistent treatment effects were observed across all lock types with no significant heterogeneity detected. ALS demonstrate statistically significant and clinically important efficacy in reducing CLABSI incidence and density while improving catheter survival in HD patients, establishing them as an essential preventive strategy in clinical practice.},
}

@article {pmid42676195,
year = {2026},
author = {Arbuzova, EE and Seksyaev, NE and Karakulova, YV and Selyanina, NV and Danilova, MA},
title = {[Atypical forms of amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {126},
number = {8},
pages = {13-20},
doi = {10.17116/jnevro202612608113},
pmid = {42676195},
issn = {1997-7298},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification ; Phenotype ; Diagnosis, Differential ; Disease Progression ; Motor Neurons/pathology ; },
abstract = {This article provides a comprehensive overview of contemporary concepts regarding the classical and atypical phenotypes of amyotrophic lateral sclerosis (ALS), with a particular focus on critical diagnostic challenges. The classical variant of the disease is characterized by the progressive involvement of both upper and lower motor neurons, typically presenting with an asymmetric onset and a predictable progression. However, several atypical phenotypes are identified, including syndromes predominantly affecting the lower motor neurons, such as the «hanging hands» and «hanging legs» syndromes, isolated bulbar paralysis, ALS with respiratory onset, and forms with a predominance of upper motor neuron involvement. These atypical variants often mimic other neurological conditions-such as cervical myelopathy, multifocal motor neuropathy, and myasthenia gravis-which can result in significant delays in the accurate diagnosis of ALS. Atypical forms of ALS represent a major source of diagnostic errors in clinical practice. Enhancing healthcare professionals' understanding of the spectrum of phenotypic presentations, alongside the application of contemporary diagnostic criteria, facilitates more timely diagnoses, optimized patient care pathways, and the prompt initiation of pathogenetic therapies, ultimately improving both survival rates and quality of life for affected individuals.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification
Phenotype
Diagnosis, Differential
Disease Progression
Motor Neurons/pathology

@article {pmid42667453,
year = {2026},
author = {Liu, C and Zhang, Y},
title = {Ginsenosides: potential therapeutic implications in neurodegenerative diseases by inhibiting ferroptosis.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42667453},
issn = {1573-4978},
mesh = {Humans ; *Ginsenosides/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Ferroptosis/drug effects ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use ; Amyotrophic Lateral Sclerosis/drug therapy ; },
abstract = {A positive correlation exists between the accelerating pace of population aging and the increasing prevalence of neurodegenerative diseases. Conditions such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) profoundly compromise patient quality of life, yet efficacious clinical interventions remain notably limited. The prevention and management of neurodegenerative diseases represent a critical global public health imperative. A comprehensive literature search was performed across PubMed, Web of Science, and Scopus to identify studies on the biological functions, molecular mechanisms, and clinical implications of ginsenosides. The search strategy incorporated MeSH terms and free-text keywords, encompassing "neurodegenerative disease", "ferroptosis", "ginsenosides", "Parkinson's disease", "Alzheimer's disease", "amyotrophic lateral sclerosis", "Huntington's disease" and "multiple sclerosis". From an initial pool of over 400 papers (1998-2026), 107 were selected in this narrative review. Ferroptosis is intricately linked to the pathogenesis of neurodegenerative diseases. Ginsenosides constitute the principal bioactive triterpenoid saponins extracted from plants of the Panax genus, demonstrating broad-spectrum pharmacological efficacy encompassing antitumor, immunomodulatory, anti‑inflammatory, anti‑allergic, anti‑atherosclerotic, antihypertensive, antidiabetic, antistress, and neuroprotective activities. Ginsenosides exert their neuroprotective effects against AD, PD, and ALS predominantly through the modulation of ferroptosis. Herein, this article provides a review of the molecular mechanisms, genetic determinants, signaling cascades, and functional implications of ferroptosis. Ginsenosides represent promising therapeutic agents in neurodegenerative diseases via modulation of iron homeostasis; this paper elucidates mechanistic insights into disease pathogenesis and evaluates their translational therapeutic potential. This narrative review highlights emerging insights that provide novel therapeutic perspectives for neurodegenerative diseases.},
}

Humans
*Ginsenosides/pharmacology/therapeutic use
*Neurodegenerative Diseases/drug therapy/metabolism
*Ferroptosis/drug effects
Animals
Neuroprotective Agents/pharmacology/therapeutic use
Amyotrophic Lateral Sclerosis/drug therapy

@article {pmid42670527,
year = {2026},
author = {Pan, L and Liu, B and Xu, J and Mu, X and Fan, L},
title = {Mesenchymal Stem Cells and Extracellular Vesicles for Neurodegenerative Diseases: Therapeutic Advances and Challenges.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {628071},
pmid = {42670527},
issn = {1178-2013},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Extracellular Vesicles/transplantation ; *Mesenchymal Stem Cells/cytology ; *Mesenchymal Stem Cell Transplantation/methods ; Animals ; },
abstract = {Mesenchymal stem cells (MSCs), as a type of adult stem cells, exhibit robust self-renewal, multi-lineage differentiation, paracrine and immunomodulatory capacities, demonstrating broad application prospects in the treatment of neurodegenerative diseases. This review systematically summarizes the mechanisms of action, therapeutic advances and comparative analyses of various MSCs and their derived extracellular vesicles (EVs) in Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and discusses the optimization effects of gene modification and pretreatment on therapeutic efficacy. This article not only highlights the advantages of various MSCs and their corresponding EVs, but also provides unique insights into their differentiated therapeutic potential and mechanism of action, which have not been fully elucidated in previous studies. Meanwhile, although current research results are encouraging, this paper also critically points out that existing studies suffer from insufficient elucidation of mechanisms and lack of large-scale clinical trials. Finally, the article prospects future directions of MSC-based therapeutic strategies, including mechanism deepening, treatment optimization and standardization system construction, to promote their translation into clinical application. However, most of the current evidence is still preclinical, and the recognized clinical efficacy in humans is still limited. This is a narrative review. Literature was screened from Web of Science and PubMed by thematic relevance and research quality, without systematic review protocol or meta-analysis.},
}

Humans
*Neurodegenerative Diseases/therapy
*Extracellular Vesicles/transplantation
*Mesenchymal Stem Cells/cytology
*Mesenchymal Stem Cell Transplantation/methods
Animals

@article {pmid42673727,
year = {2026},
author = {Aladwan, S and Jasim, A and Qassem, TA and Gajjar, TB and Hanumanthayya, M and Tripathi, V and Maharana, L and Bainsal, N},
title = {Human health risk assessment of toxic and non-toxic elements in various oily, cream, and powder cosmetics in Arab countries- A systematic literature review.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {97},
number = {},
pages = {127946},
doi = {10.1016/j.jtemb.2026.127946},
pmid = {42673727},
issn = {1878-3252},
abstract = {Oily, cream, and powder cosmetics (OCPCs) are widely used worldwide, especially in Arab nations, highlighting the need for ongoing heavy metal (HM) monitoring. This systematic review examined 16 HM concentrations in 14 OCPC product categories across 11 of the 22 Arab countries, selected countries based on predefined inclusion and exclusion criteria, and evaluated their associated health risks for only 9 of the 14 OCPCs for which sufficient data were available. The analysis included 24 papers published between June 1, 2007, and January 30, 2026, selected according to prescribed inclusion and exclusion criteria. International authorities like the WHO and the EU set acceptable limits (ALs) for HM levels. According to EPA criteria, all detected HMs underwent a health risk assessment (HRA). Saudi Arabia and Jordan had the highest HM detection rates in OCPCs among the 11 Arab countries analyzed, underscoring the need for stronger regulation. Moisturizing creams, toners, cosmetic masks, and oils were mostly contaminated with non-toxic HMs, whereas facial foundation and face cream samples were contaminated with toxic HMs. Despite exceedances of WHO and EU ALs for several elements, the EPA-based dermal risk indices remained below acceptable thresholds, reflecting the distinction between concentration-based regulatory limits and exposure-based health risk assessment. Arab regulatory agencies should establish monitoring systems to limit HMs in OCPCs, in line with WHO and EU guidelines on HM ALs in cosmetics, before market access.},
}

@article {pmid42675240,
year = {2026},
author = {Ma, S and Luo, S and Zhong, H},
title = {Artificial Intelligence in Neuromuscular Diseases: Opportunities for a Data-Scarce Field.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42675240},
issn = {2193-8253},
support = {Open research fund: gect-2025-Z01//Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases/ ; },
abstract = {Neuromuscular diseases (NMDs) encompass over 800 distinct entities affecting approximately one in 1000 individuals worldwide, with progressive muscle weakness, atrophy, and motor impairment as primary clinical manifestations. The rarity of most NMDs creates fundamental challenges for artificial intelligence (AI) and machine learning (ML) applications that typically require large-scale datasets. In this narrative review we synthesize the literature published between 2018 and 2025 on AI applications across the NMD spectrum, organized by clinical application domain. We examine how AI has advanced diagnostic capabilities through genetic variant interpretation, muscle magnetic resonance imaging analysis, electromyography-based classification, and computational pathology. In disease monitoring and prognosis, wearable-derived digital biomarkers have achieved regulatory qualification (US Food and Drug Administration [FDA] and European Medicines Agency [EMA]) as clinical trial endpoints for Duchenne muscular dystrophy, while AI-driven survival models for amyotrophic lateral sclerosis (ALS) have been validated across 14 European centers. Proteomic and multi-omics analyses using ML have identified diagnostic panels for ALS. However, most reported models were developed and internally validated on single-center datasets, and few have undergone external or prospective validation or clinical implementation. Despite these achievements, research intensity varies dramatically across NMD subtypes, with ALS and Duchenne muscular dystrophy dominating while myotonic dystrophy, congenital myopathies, and metabolic myopathies remain virtually unexplored. Critical gaps persist in computational pathology, multi-center validation, and clinical translation. In this review, we discuss how federated learning, international collaborative networks (TREAT-NMD, Solve-RD, EURO-NMD), and foundation models can address these challenges, and propose directions for future AI-enhanced clinical studies in this data-scarce field.},
}

@article {pmid42656917,
year = {2026},
author = {Zhang, J and Tang, P and Huang, L and Lv, J and Chen, Y and Wang, Y and Luo, Y},
title = {Multifaceted roles of S100A6 in neurological disorders: expression, interaction networks, and clinical implications.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1890559},
pmid = {42656917},
issn = {1663-9812},
abstract = {S100A6 (calcyclin) is a multifunctional Ca[2+]/Zn[2+]-binding protein of the S100 family, widely expressed in neurons and glia with a developmentally regulated and cell-type-specific pattern. This review synthesizes current knowledge on its roles in the nervous system. We detail its complex interactome, which includes cytoskeletal regulators, molecular chaperones, nuclear transport proteins, and cell surface receptors, positioning S100A6 as a central signaling hub. Furthermore, we examine its dynamic and context-dependent involvement in major neurological disorders. In Alzheimer's disease and amyotrophic lateral sclerosis, it functions as a glial-derived factor linking protein aggregation, metal dyshomeostasis, and neuroinflammation. In neuro-oncology, S100A6 exhibits dual roles, acting as a promoter of malignancy and immunosuppression in glioblastoma, an epigenetically silenced marker in medulloblastoma, and a diagnostic aid for peripheral nerve sheath tumors. Its expression is also altered in epilepsy, traumatic brain injury, and autoimmune encephalitis. Understanding the nuanced functions of S100A6 offers significant potential for developing novel diagnostic biomarkers and targeted therapeutic strategies for a range of challenging neurological conditions.},
}

@article {pmid42657487,
year = {2026},
author = {da Silva, AA and Pupe, CCB and Dos Santos, JCC},
title = {High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2026.2713755},
pmid = {42657487},
issn = {1758-2032},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder characterized by selective degeneration of upper and lower motor neurons, driven by converging mechanisms including glutamatergic excitotoxicity, mitochondrial dysfunction, oxidative stress, calcium dyshomeostasis, impaired RNA metabolism, and neuroinflammation. In the absence of effective disease-modifying therapies, high-dose methylcobalamin has emerged as a candidate intervention based on its pleiotropic neurobiological effects. A structured literature search was conducted in PubMed/MEDLINE and ScienceDirect to identify peer-reviewed studies published between January 2017 and December 2025 addressing the mechanistic, preclinical, and clinical effects of methylcobalamin in ALS. Preclinical evidence suggests that methylcobalamin modulates homocysteine metabolism, supports S-adenosylmethionine-dependent methylation pathways, preserves mitochondrial integrity, attenuates oxidative stress, and promotes axonal regeneration. Experimental and translational findings further indicate that its therapeutic effects may be strongly dose dependent, particularly under ultra-high-dose regimens capable of overcoming limitations in central nervous system delivery. Clinical trials evaluating ultra-high-dose methylcobalamin demonstrate a potential attenuation of functional decline in patients treated during early disease stages, although effects on survival and respiratory outcomes remain inconsistent. This narrative review integrates molecular mechanisms, experimental evidence, biomarker research, and clinical trial data to examine the translational relevance, stage dependency, and therapeutic implications of high-dose methylcobalamin in ALS.},
}

@article {pmid42661656,
year = {2026},
author = {Praharaj, S and Chakraborty, E and Mahalingam, G},
title = {Ultraviolet radiation and neurodegeneration: molecular mechanisms underlying dual neuroprotective and neurotoxic effects.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1909393},
pmid = {42661656},
issn = {1662-5102},
abstract = {Ultraviolet radiation exhibits a complex, often contradictory link to neurodegeneration risk/progression, spanning clinically diagnosed diseases [Parkinson's Disease (PD), Alzheimer's Disease (AD), Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS)] or intermediate phenotypes (decreased neurogenesis, loss of hippocampal volume). The aim of this review is to highlight the dual impact of UV radiation by collecting and synthesizing experimental (preclinical and translational) evidence as well as epidemiological evidence. Current literature exhibits a clear dichotomy: while Vitamin D is capable of exerting a potent neuroprotective effect via anti-oxidant and anti-inflammatory pathways, chronic and intense UV radiation exposure actually hastens the progression or even drives neurodegeneration via a variety of mechanisms. UV radiation exerts its effects through various interconnected pathways: DNA damage pathways, ROS mediated pathways, vitamin D signaling and the skin-brain axis, which unifies both protective and degenerative effects of UV radiation. Owing to the increasing occurrence of neurodegenerative diseases in the general population, these pathways and mechanisms must be leveraged in future research to develop novel therapeutic and preventive strategies. Investigation of biomarkers linked to certain genetic and environmental factors that could provide a link to predisposition toward neurodegeneration and standardization of UV radiation dosimetry (exposure dose/duration) across experimental or pre-clinical studies must also be prioritized.},
}

@article {pmid42666355,
year = {2026},
author = {Wei, Y and Wang, J and Ji, Y and Shang, T and Shen, Y and Sun, H and Cai, Y},
title = {Therapeutic Challenges and Future Breakthroughs in Amyotrophic Lateral Sclerosis: From Precision Medicine to Innovative Trial Design.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {626069},
pmid = {42666355},
issn = {1177-8881},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Precision Medicine ; Animals ; *Clinical Trials as Topic ; *Neuroprotective Agents/therapeutic use ; *Research Design ; Genetic Therapy ; Drug Development ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous and fatal neurodegenerative disorder, for which clinical management and drug development have long faced formidable challenges. Since the approval of riluzole and edaravone, dozens of promising drug candidates that showed efficacy in preclinical models have failed in Phase III trials, highlighting an urgent need for systematic re-evaluation of the field. This review provides a comprehensive summary of the major limitations of current clinical therapies for ALS. These include the modest survival benefit of riluzole, the narrow eligible population for edaravone, and the complex trajectory of sodium phenylbutyrate-taurursodiol, which received accelerated approval but was subsequently voluntarily withdrawn after its confirmatory Phase III trial failed to meet its primary endpoints. On this basis, we discuss four major challenges that contribute to clinical trial failures: disease heterogeneity, paucity of reliable biomarkers, insufficient translational validity of preclinical models, and inherent flaws in conventional trial designs. Subsequently, we discuss emerging therapeutic strategies, encompassing precision medicine and gene therapy (exemplified by the development of the antisense oligonucleotide tofersen for SOD1-ALS), targeting protein homeostasis, modulation of neuroinflammation, metabolic and energetic support, neuroprotection and regeneration, as well as multi-target combination approaches. Innovative trial designs, including adaptive platform trials (exemplified by the HEALEY ALS Platform Trial), enrichment designs, sequential designs, N-of-1 trials, and virtual clinical trials are fundamentally reshaping the drug development paradigm in ALS. In conclusion, ALS treatment is at a historic turning point from a "one-size-fits-all" approach toward "precisely stratified" medicine. Future success depends on establishing multimodal biomarker panels, implementing genetic testing-guided individualized therapy, developing combination regimens, and integrating patient-reported outcomes with palliative care. Although substantial challenges remain, the clinical success of Tofersen provides evidence that precision therapeutic strategies may gradually transform ALS management toward a more individualized and disease-modifying approach.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/therapy
Humans
*Precision Medicine
Animals
*Clinical Trials as Topic
*Neuroprotective Agents/therapeutic use
*Research Design
Genetic Therapy
Drug Development

@article {pmid42653407,
year = {2026},
author = {Rosenfeld, J and Salomon-Zimri, S and Tracik, F},
title = {Combination Pharmacology for ALS: A Mechanistic Rationale.},
journal = {International journal of molecular sciences},
volume = {27},
number = {16},
pages = {},
pmid = {42653407},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Drug Therapy, Combination ; Oxidative Stress/drug effects ; Mitochondria/metabolism/drug effects ; },
abstract = {Amyotrophic lateral sclerosis (ALS) involves multiple converging pathogenic mechanisms, including glutamate excitotoxicity, oxidative and endoplasmic-reticulum stress, mitochondrial dysfunction, neuroinflammation, iron dysregulation, and altered microRNA processing. Expecting a single pharmacologic intervention to meaningfully alter such a complex disease has proven overly optimistic and is reflected by the modest clinical benefits of approved monotherapies. This review outlines the mechanistic foundation and translational rationale for combination pharmacology in ALS. Drawing from paradigms in oncology, infectious disease, and other neurological disorders, it explores how rational multi-target strategies, whether synergistic, complementary, or pathway-divergent, may better address the multifactorial biology of ALS. The review also discusses recent mechanistic examples and design principles for advancing this therapeutic paradigm.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology
Animals
Drug Therapy, Combination
Oxidative Stress/drug effects
Mitochondria/metabolism/drug effects

@article {pmid42656624,
year = {2026},
author = {Soberano, JI and Montayre, J},
title = {Social frailty and related social vulnerabilities among older adults in the Philippines: A narrative review.},
journal = {International journal of nursing studies advances},
volume = {11},
number = {},
pages = {100655},
pmid = {42656624},
issn = {2666-142X},
abstract = {OBJECTIVES: To synthesize the evidence on social frailty among older adults in the Philippines, with attention to sociocultural and structural determinants, assessment approaches, and policy and program responses, and to derive implications for nursing practice and research.

METHODS: A narrative review with scoping elements was informed by the Scale for the Assessment of Narrative Review Articles (SANRA), with selected PRISMA-ScR items used to enhance reporting transparency. Electronic searches of PubMed, CINAHL, Web of Science, PsycINFO, and Google Scholar identified peer-reviewed and relevant verifiable discussion papers written in English from January 2015 to December 2025 (final search: 5 January 2026). The search, title, and abstract screening, full-text review, and data extraction were performed independently by two reviewers, with disagreements resolved through consensus. Eligible studies focused on community-dwelling Filipinos aged ≥60 years and examined social frailty or closely related constructs, including social networks, participation, support, isolation, loneliness, and social determinants of health and functioning. Data were synthesized thematically using Bunt et al.'s four domains of social frailty.

RESULTS: Thirty-five studies were included, most using qualitative or cross-sectional designs. Evidence clustered in the domains of general resources and social behavior activities, particularly access, participation, mobility, disaster related disruption, and emerging digital engagement. Fewer studies addressed social resources and self-management abilities. Family, kinship, and faith-based networks, and community organization were important protective systems, but were increasingly strained by migration, economic insecurity, service limitations, and environmental disruption.

CONCLUSIONS: Social frailty among older Filipinos emerges at the intersection of structural disadvantage, changing informal support systems, community participation, digital access, and self-management capacities. Addressing social frailty requires multidimensional assessment, culturally grounded measurement, and coordinated nursing, community and policy responses.},
}

@article {pmid42652600,
year = {2026},
author = {Davies, A and Bentley, A and Bikov, A},
title = {The Role of Neurofilaments in Diagnosis and Monitoring of Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {16},
pages = {},
pmid = {42652600},
issn = {2077-0383},
abstract = {Background: Amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is a devastating diagnosis that often leads to mortality within 2-5 years of symptom onset. Respiratory failure and aspiration pneumonia both associated with respiratory muscle weakness are the most common causes of death. Difficult to diagnose and devastating in its prognosis, much research has aimed to identify a reliable biomarker to diagnose ALS, prognosticate and improve enrolment into clinical trials to further research efforts. Over the last few decades, neurofilaments (NFs) have emerged as promising biomarkers, especially neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). This review aims to summarise the current evidence for use of NFs as biomarkers in ALS. Current Evidence: Higher levels of NFL and pNFH are measured in CSF than in serum, and levels in CSF and serum are correlated. High CSF NFL, serum NFL and CSF pNFH levels could differentiate patients with ALS from healthy controls, other neurological disease, neurodegenerative controls (without MND), other MND subtypes and ALS disease mimics; however, studies reported a high degree of heterogeneity irrespective of which media or NFs have been used. The number of studies examining NFs to predict respiratory failure in patients with ALS is low. Conclusions and Future Directions: Despite numerous studies consistently reporting higher NF levels in ALS compared to various controls, their clinical value is limited due to high heterogeneity of the results and inconsistencies in proving its prognostic value. Further understanding the relationship between NF levels and respiratory failure is paramount to improve the quality of life of patients with ALS and increase survival.},
}

@article {pmid42653169,
year = {2026},
author = {Terribile, G and Pedrinazzi, M and Frigerio, I and Sancini, G and Combi, R},
title = {Theranostic Innovative Strategies for Brain Diseases: New Insights on Neurovascular Unit-Associated Pathological Changes in Neurodegenerative Disorders and Aging.},
journal = {International journal of molecular sciences},
volume = {27},
number = {16},
pages = {},
pmid = {42653169},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology/diagnosis ; *Aging/pathology ; Animals ; Blood-Brain Barrier/metabolism/pathology ; *Theranostic Nanomedicine/methods ; *Brain Diseases/therapy/diagnosis/pathology ; Nanoparticles ; MicroRNAs/genetics ; Nanotechnology ; },
abstract = {Central nervous system (CNS) disorders represent a significant healthcare challenge, with aging as the primary risk factor. Current clinical management remains predominantly symptomatic, as late-stage diagnosis and the blood-brain barrier (BBB) limit therapeutic efficacy. This review synthesizes emerging innovations in neurotheranostics-integrated diagnostic and therapeutic platforms-focusing on the neurovascular unit (NVU) as a central pathogenic driver and target. Evidence indicates that NVU and BBB dysfunction are early events in Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases, often preceding classic neuropathological hallmarks. The review highlights the potential of nanotechnology, engineered nanoparticles (NPs) and microRNAs (miRNAs) as precision tools for early detection and targeted CNS delivery. Additionally, it discusses the transformative impact of artificial intelligence (AI) in facilitating personalized, predictive care. Transitioning from a generic "one-pill-for-one-disease" model to a patient-centered strategy targeting early NVU alterations is essential. Integrating AI, nanotechnology and NVU-focused strategies offers a promising path toward effective, personalized disease-modifying therapies.},
}

Humans
*Neurodegenerative Diseases/therapy/pathology/diagnosis
*Aging/pathology
Animals
Blood-Brain Barrier/metabolism/pathology
*Theranostic Nanomedicine/methods
*Brain Diseases/therapy/diagnosis/pathology
Nanoparticles
MicroRNAs/genetics
Nanotechnology

@article {pmid42652164,
year = {2026},
author = {Karbownik, M and Fidura, M and Perlikowska, R},
title = {Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?.},
journal = {Biomedicines},
volume = {14},
number = {8},
pages = {},
pmid = {42652164},
issn = {2227-9059},
support = {564-20-100//Medical University of Lodz/ ; },
abstract = {Canonical signal peptides (SPs) are short N-terminal sequences that direct nascent proteins into the secretory pathway, but their role extends far beyond protein targeting. Advances in sequencing and computational tools have enabled their systematic identification across proteomes, highlighting SPs as critical regulators of protein biogenesis, including endoplasmic reticulum (ER) targeting, translocation, folding, and proteostasis. Clinically, mutations affecting SP function underlie a distinct group of human disorders, while SP-derived fragments are emerging as diagnostic biomarkers and therapeutic targets. In biotechnology, SPs are engineered to enhance recombinant protein production and serve as molecular tags for intracellular delivery. Together, these developments position SPs at the intersection of fundamental cell biology, medicine, and biotechnology. While this review primarily focuses on canonical SPs, it also considers selected non-canonical targeting and topogenic sequences whose dysfunction contributes to protein misfolding, impaired ER translocation, disrupted degradation pathways, and altered intracellular trafficking in neurodegenerative diseases. Aberrations involving both conventional SPs and alternative targeting/topogenic elements contribute to pathological protein aggregation, a hallmark of major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington Disease (HD), prion diseases, and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); in multiple sclerosis (MS) is primarily an inflammatory demyelinating disease, where abnormal protein exposure, potentially linked to misprocessed SPs, can activate immune responses. By synthesizing current knowledge, the review explores how alterations in targeting determinants influence key proteostasis pathways, acting as upstream modulators of disease-relevant molecular cascades. It further discusses the emerging concept that SP-derived fragments may participate in intercellular communication, adding an additional layer of regulatory complexity.},
}

@article {pmid42642835,
year = {2026},
author = {Aldaghi, FS and Siahpoosh, Z and Salehi, Z and Mashayekhi, F and Sohrabnezhad, S},
title = {Unraveling Neurodegeneration: Common Molecular Mechanisms and Novel Therapeutic Concepts in Major Neurodegenerative Disorders.},
journal = {Brain and behavior},
volume = {16},
number = {8},
pages = {e71615},
pmid = {42642835},
issn = {2162-3279},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy ; Oxidative Stress/physiology ; Animals ; *Neuroinflammatory Diseases/metabolism ; Mitochondria/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; Alzheimer Disease/metabolism ; Multiple Sclerosis/metabolism ; Parkinson Disease/metabolism ; Huntington Disease/metabolism ; Inflammasomes/metabolism ; },
abstract = {PURPOSE: Although Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD) present with markedly different clinical phenotypes, these neurodegenerative diseases (NDDs) appear to converge on a shared set of underlying molecular disturbances. This review sought to integrate disease-specific causative triggers with shared pathogenic pathways, focusing on neuroinflammatory signaling, oxidative imbalance, mitochondrial impairment, and disrupted protein homeostasis, in order to support multi-target, disease-modifying therapeutic strategies.

METHOD: Relevant classical and contemporary literature, encompassing original research and review articles on the molecular basis of AD, PD, ALS, MS, and HD, was reviewed and synthesized narratively, with attention to how neuroinflammatory and oxidative stress pathways intersect, reinforce one another through mitochondrial and inflammasome-driven feedback, and recur across the five conditions.

FINDING: In each disorder, persistently activated microglia and astrocytes secreted inflammatory mediators and reactive oxygen species, engaged the NLRP3 inflammasome, and progressively destabilized cellular homeostasis through a self-perpetuating cycle linking neuroinflammation and oxidative stress. Disease-specific lesions nonetheless persisted: amyloid-β and tau pathology in AD; α-synuclein aggregation with iron-driven mitochondrial damage in PD; RNA-binding protein dysfunction, proteostatic collapse, and excitotoxicity in ALS; inflammatory demyelination and axonal bioenergetic failure in MS; and mutant huntingtin-driven transcriptional and mitochondrial disruption in HD. These distinct triggers ultimately converged on shared downstream cascades.

CONCLUSION: Recognizing this shared pathogenic foundation supports multi-target therapies-such as Nrf2 activation, NLRP3 inhibition, mitochondria-targeted antioxidants, and gene-based interventions-that extend across diagnostic boundaries, though challenges in intervention timing, patient stratification, and clinical translation remain unresolved.},
}

Humans
*Neurodegenerative Diseases/metabolism/therapy
Oxidative Stress/physiology
Animals
*Neuroinflammatory Diseases/metabolism
Mitochondria/metabolism
Amyotrophic Lateral Sclerosis/metabolism
Alzheimer Disease/metabolism
Multiple Sclerosis/metabolism
Parkinson Disease/metabolism
Huntington Disease/metabolism
Inflammasomes/metabolism

@article {pmid42643197,
year = {2026},
author = {Sigala, N and Cobandag, M and Leppard, L and Medford, N},
title = {Insight and executive functions in acquired brain injury: empirical evidence and theoretical frameworks.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1884495},
pmid = {42643197},
issn = {1664-2295},
mesh = {Humans ; *Brain Injuries/physiopathology/psychology/complications ; *Executive Function/physiology ; *Awareness/physiology ; *Prefrontal Cortex/physiopathology ; Cognitive Flexibility ; },
abstract = {Impaired self-awareness affects 30-50% of patients with moderate to severe acquired brain injury (ABI) and represents one of the most clinically consequential obstacles to effective rehabilitation. Despite substantial evidence that self-awareness and executive functions share neural substrates in prefrontal cortex, the mechanisms linking these two functions remain incompletely specified. This paper reviews the empirical evidence for the relationship between executive functions and insight in ABI, and evaluates four theoretical frameworks: the Cognitive Awareness Model, the Dynamic Comprehensive Model of Awareness, Mograbi et al.'s predictive coding framework, and Duncan's adaptive coding model. It then proposes a novel integration of the latter two as a mechanistically grounded account of why executive dysfunction and impaired self-awareness co-occur following prefrontal damage. We argue that adaptive coding describes the representational flexibility of prefrontal neurons in coding self-relevant information, whilst predictive coding provides the computational logic, driven by precision-weighted prediction errors, through which this adaptive selection is updated. We conclude by discussing assessment and rehabilitation implications in ABI.},
}

Humans
*Brain Injuries/physiopathology/psychology/complications
*Executive Function/physiology
*Awareness/physiology
*Prefrontal Cortex/physiopathology
Cognitive Flexibility

@article {pmid42645160,
year = {2026},
author = {Leggett, S and Sanghai, N and Ru, C and Marcogliese, PC and Tranmer, GK},
title = {Drosophila: An Emerging New Approach Method (NAM) for Studying Amyotrophic Lateral Sclerosis (ALS).},
journal = {Cells},
volume = {15},
number = {16},
pages = {},
pmid = {42645160},
issn = {2073-4409},
support = {202210PJT-495295/CAPMC/CIHR/Canada ; RGPIN-2017-05938//Natural Sciences and Engineering Research Council of Canada/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/drug therapy/metabolism ; *Drosophila melanogaster/genetics/metabolism ; Humans ; Disease Models, Animal ; DNA-Binding Proteins/metabolism/genetics ; Superoxide Dismutase-1/metabolism/genetics ; Drug Evaluation, Preclinical ; },
abstract = {Drosophila melanogaster (D. melanogaster), or fruit flies, are a commonly used model organism in the study of neurodegenerative diseases (NDs). Their short lifespan, low cost, genetic tractability, and conserved signaling and developmental pathways make them ideal for studying NDs and associated biochemical pathways. Further, flies offer the advantage of high-throughput exploratory drug and genetic screening without stringent ethical constraints. Therefore, D. melanogaster serves as an ideal organism for preliminary drug screening before transitioning to toxicity and efficacy studies in vertebrate models. Following the recent plan by the United States FDA (US FDA) and the National Institutes of Health (NIH) to progressively phase out preclinical drug testing in vertebrate animals and introduce New Approach Methodologies (NAMs), D. melanogaster has the potential to become part of the conventional drug testing pipeline in the future. This literature review focuses on the use of D. melanogaster models as a powerful, low-cost model organism to study superoxide dismutase 1 (SOD1)- and TAR DNA-binding protein 43 (TDP-43)-linked Amyotrophic Lateral Sclerosis (ALS), as well as previous efforts to screen drugs in SOD1- and TDP-43-expressing Drosophila models.},
}

Animals
*Amyotrophic Lateral Sclerosis/genetics/pathology/drug therapy/metabolism
*Drosophila melanogaster/genetics/metabolism
Humans
Disease Models, Animal
DNA-Binding Proteins/metabolism/genetics
Superoxide Dismutase-1/metabolism/genetics
Drug Evaluation, Preclinical

@article {pmid42646366,
year = {2026},
author = {Anwar, AI and Hegazi, AA and Bhuchakra, HP and Nelson, JR and Birdsong, TL and Fontenot, CJ and Zeibo, M and Fazal-Ur-Rehman, MM and Bieber, HP and Spring, CJ and Smith, JL and Hachem, IA and Singh, T and Sawaya, MF and Murnane, KS and Kaye, AD},
title = {Pridopidine Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases.},
journal = {Neurology international},
volume = {18},
number = {8},
pages = {},
pmid = {42646366},
issn = {2035-8385},
abstract = {Neurodegenerative diseases are targets for pridopidine therapy, which aims to improve quality of life through neuroprotective mechanisms that involve sigma-1 receptor (S1R) activation. Neurodegenerative motor and cognitive diseases are influenced by dopamine imbalance, where disruptions in pathways contribute to states that are hyperkinetic or hypokinetic, while current dopaminergic treatments are symptomatic rather than disease-modifying, especially for Huntington's disease and Amyotrophic lateral sclerosis. This review summarizes the mechanisms underlying pridopidine-mediated neuroprotection and examines the current evidence supporting its therapeutic potential. The S1R is an endoplasmic reticulum-mitochondria-associated chaperone involved in homeostasis of calcium, stress regulation, and mitochondrial function. Pridopidine is a small lipophilic molecule that crosses the blood-brain barrier and acts as an S1R agonist, with minimal dopamine D2 receptor occupancy. Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington's disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy.},
}

@article {pmid42646579,
year = {2026},
author = {Calabrò, RS and Calderone, A and Ravi, D and Galipò, C and Crupi, MF and Quartarone, A},
title = {Hospital-to-Home Neurological Transition Care: A Scoping Review Across Selected Chronic Neurological Disorders.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {42646579},
issn = {2076-3271},
mesh = {Humans ; *Nervous System Diseases/therapy ; *Transitional Care ; Multiple Sclerosis ; Hospitalization ; Chronic Disease ; Amyotrophic Lateral Sclerosis ; },
abstract = {BACKGROUND: Returning home after neurological hospitalization, rehabilitation, or specialist care transfers responsibility to patients, caregivers, and community services. We mapped mechanisms and gaps across dementia/Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).

METHODS: Following JBI guidance and PRISMA-ScR, eligibility was derived using population-concept-context. We included empirical reports involving adults with a target condition, a post-discharge, return-home, rehabilitation, telehealth, caregiver, treatment, respiratory, or palliative continuity component, and post-transition patient, caregiver, service, safety, rehabilitation, equity, or implementation outcomes. Five databases were searched through to 11 May 2026. Two reviewers independently screened records; charting and classification were verified by R.S.C., A.C., and A.Q.

RESULTS: Of 24,417 records, 69 reports were included: Dementia/ADRD, 28; PD, 10; MS, 9; and ALS, 22. Eighteen were core transition reports (26.1%), 14 return-home/community re-entry reports (20.3%), 16 adjacent continuity reports (23.2%), and 21 companion/secondary reports (30.4%). Dementia/ADRD provided discharge-anchored evidence; PD and MS mapped functional carry-over; ALS mapped adjacent respiratory, telehealth, and palliative continuity.

CONCLUSIONS: The main contribution is an operational cross-disease framework separating direct discharge, return-home, adjacent-continuity, and companion evidence while linking mechanisms to disease-specific pathways. This framework maps disease-specific functions, not comparative effectiveness. The proposed frameworks are author-derived and hypothesis-generating. Future studies should use explicit anchors, standardized outcomes, longer follow-up, and equity-sensitive implementation measures addressing caregiver workload, digital access, feasibility, and sustainability. They inform testable, context-sensitive intervention designs for future neurological transition-care research and practice.},
}

Humans
*Nervous System Diseases/therapy
*Transitional Care
Multiple Sclerosis
Hospitalization
Chronic Disease
Amyotrophic Lateral Sclerosis

@article {pmid42647236,
year = {2026},
author = {Sanchis-Sanchis, E and de la Rubia Ortí, JE and Sancho-Cantus, D and Cunha-Pérez, C and Casaña-Mohedo, J},
title = {The Microbiota-Gut-Brain Axis and Nutritional Interventions in Amyotrophic Lateral Sclerosis: Pathophysiological Mechanisms, Neuroinflammation, and Non-Motor Manifestations-Scoping Review.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {33},
number = {3},
pages = {},
pmid = {42647236},
issn = {1873-149X},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder in which systemic pathophysiological alterations significantly contribute to disease progression and non-motor manifestations, such as depression and anxiety. The microbiota-gut-brain axis represents a critical bidirectional pathway in which intestinal dysbiosis and epithelial barrier disruption catalyze central neuroinflammation. This scoping review synthesizes evidence from 43 empirical and analytical studies across 28 countries and maps the findings under the WHO International Classification of Functioning (ICF) framework. Pathophysiological data reveal a profound taxonomic shift in patients with ALS, characterized by severe depletion of neuroprotective, butyrate-producing genera (Akkermansia and Prevotella) and enrichment of pro-inflammatory Enterobacteriaceae. This dysbiotic state leads to structural damage to the intestinal mucosa, alteration of Paneth cells, and downregulation of tight junction proteins (zonulin), triggering a "leaky gut" phenomenon. Subsequent systemic translocation of lipopolysaccharides (LPS) induces TLR4-mediated endotoxemia, microglial hyperactivation, and accelerated motor neuron apoptosis. Conversely, therapeutic modulation via Fecal Microbiota Transplantation (FMT), psychobiotics, and metabolic interventions (ketogenic or Mediterranean diets) has demonstrated significant efficacy in restoring epithelial integrity, mitigating mitochondrial hypermetabolism, and reducing emotional distress. This review identifies a critical research gap in the microstructural characterization of the enteric nervous system in ALS. Incorporating microbiome-targeted biomarkers into clinical protocols is crucial for implementing a stratified, multi-systemic therapeutic strategy aimed at enhancing patient prognosis and psychological well-being.},
}

@article {pmid42650212,
year = {2026},
author = {Varrassi, G and Tran, YV and Farì, G and Narvaez Encinas, M and Corriero, A and Puntillo, F and Pham, PV and Leoni, MLG},
title = {The Eye as a Window to Neurodegeneration: Oxidative Stress, Optic Nerve Vulnerability, and Retinal Biomarkers-A Scoping Review.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/antiox15080948},
pmid = {42650212},
issn = {2076-3921},
support = {//Tam Anh General Hospital, Ha Noi/ ; },
abstract = {Neurodegenerative diseases represent a major and growing global health burden characterized by progressive neuronal dysfunction, axonal degeneration, and irreversible neural tissue loss. Increasing evidence identifies oxidative stress as one of several interacting pathogenic mechanisms in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and several optic neuropathies. Interest has increasingly focused on the brain-retina axis, as the retina and optic nerve share structural, metabolic, and molecular features with the central nervous system and may provide accessible insights into neurodegeneration. This scoping review mapped current evidence on oxidative stress in neurodegeneration, emphasizing cranial nerve involvement, optic nerve vulnerability, retinal ganglion cell degeneration, visual dysfunction, oxidative biomarkers, and emerging therapeutic strategies. The review followed established methodological frameworks and PRISMA-ScR recommendations; no formal risk-of-bias appraisal was undertaken, consistent with scoping-review methodology. The literature shows that oxidative stress interacts with mitochondrial dysfunction, neuroinflammation, impaired mitophagy, ferroptosis, and altered bioenergetics, contributing to neuronal injury in cerebral and retinal disorders. Retinal ganglion cells appear particularly vulnerable because of their high metabolic demands and reliance on oxidative phosphorylation. Glaucoma and other optic neuropathies share molecular signatures with central neurodegenerative diseases. Retinal imaging and oxidative biomarkers show promise for diagnosis, monitoring, and stratification. The evidence base is nonetheless dominated by preclinical work; biomarker performance is inconsistent across matrices and assay platforms and most antioxidant clinical trials have been negative. Oxidative stress is therefore best regarded as one interacting node of a broader pathogenic network rather than a universal or predominant driver and the brain-retina continuum as a mechanistically plausible but not yet clinically validated framework for biomarker-guided neuroprotection.},
}

@article {pmid42650794,
year = {2026},
author = {Mitsumoto, H and Blasco, H and Corcia, P and Silani, V},
title = {ALS: An Organism-Wide Bioenergetic Failure Due to Mitochondrial Dysfunctions?.},
journal = {Biomolecules},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/biom16081126},
pmid = {42650794},
issn = {2218-273X},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Mitochondria/metabolism/pathology ; *Energy Metabolism ; Animals ; Oxidative Stress ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating and invariably fatal disease for which currently available disease-modifying therapies provide only modest benefit. Defining its underlying pathogenesis is therefore essential for the development of effective treatments. Increasing evidence indicates that ALS is not restricted to motor neurons but involves multiple neuronal and glial systems, extending to peripheral organs, often at subclinical levels. These multisystem alterations may precede overt neurological symptoms by years and are accompanied by metabolic disturbances, including progressive weight loss and hypermetabolism. In peripheral tissues, ongoing cellular turnover and associated immune and inflammatory responses may further increase energy demand. Within this framework, mitochondrial dysfunction emerges as a central mechanism underlying impaired bioenergetics and systemic metabolic failure. Mitochondria not only regulate energy production but also contribute to oxidative stress, which in turn exacerbates mitochondrial injury, creating a self-amplifying cycle. Importantly, many genetic forms of familial ALS directly affect mitochondrial pathways, and similar biochemical abnormalities are observed in sporadic ALS. These shared features suggest that mitochondrial dysfunction represents a common pathway across ALS subtypes. Targeting upstream mechanisms of mitochondrial impairment may therefore provide a unifying strategy for understanding ALS pathogenesis and developing effective therapies.},
}

*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
Humans
*Mitochondria/metabolism/pathology
*Energy Metabolism
Animals
Oxidative Stress

@article {pmid42650874,
year = {2026},
author = {Wang, Z and Fu, Y and Li, S and Zhang, Y and Sun, T and Miao, N},
title = {The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.},
journal = {Biomolecules},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/biom16081208},
pmid = {42650874},
issn = {2218-273X},
mesh = {Humans ; *RNA, Long Noncoding/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; RNA, Competitive Endogenous ; Animals ; *Gene Regulatory Networks ; *Motor Neuron Disease/genetics/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Muscular Atrophy, Spinal/genetics/pathology/metabolism ; },
abstract = {Motor neurons form a highly specialized network composed of α-, β-, and γ-subtypes that coordinate skeletal muscle activity. Motor neuron diseases (MNDs), including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are characterized by the progressive degeneration of this network, resulting in motor dysfunction. Emerging evidence underscores the significant roles of long non-coding RNAs (lncRNAs) in motor neuron development and disease. However, only a few have been experimentally confirmed as true ceRNA regulators, highlighting the need to differentiate validated mechanisms from mere associations or predictions. This review summarizes the regulatory roles of lncRNA-associated ceRNA networks in motor neuron development, evaluates the evidence for their involvement in MNDs, and explores their potential impact on disease progression. It also addresses current challenges, knowledge gaps, and future research directions for understanding ceRNA-mediated mechanisms and developing therapeutic strategies for MNDs.},
}

Humans
*RNA, Long Noncoding/genetics/metabolism
*Motor Neurons/metabolism/pathology
RNA, Competitive Endogenous
Animals
*Gene Regulatory Networks
*Motor Neuron Disease/genetics/pathology/metabolism
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
*Muscular Atrophy, Spinal/genetics/pathology/metabolism

@article {pmid42651103,
year = {2026},
author = {Costa, IM and Kanashiro, A and Barros, GSF and Monteiro, AJ and Bonilha, CS and Galdino, G and Veras, FP},
title = {Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/brainsci16080792},
pmid = {42651103},
issn = {2076-3425},
abstract = {Neuroinflammation is a complex process involved in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Neutrophils, although traditionally considered peripheral immune cells, have emerged as active participants in the immunopathology of the central nervous system (CNS) through the release of neutrophil extracellular traps (NETs), structures composed of decondensed chromatin embedded with pro-inflammatory proteins. Evidence suggests that NETs play a dual role: they are protective against pathogens but can also induce tissue damage when produced in excess. Several pathways are involved in their formation, including vesicle-mediated release (vital NETs), the lytic NADPH oxidase (NOX)-dependent pathway, and the mitochondrial pathway. Targeting NETs therapeutically, through the use of NETosis inhibitors, NET-degrading strategies, or blockade of neutrophil migration, has shown promise in reducing neuroinflammation/neurodegeneration and improving neurological outcomes in experimental models. This review aims to investigate both the protective and deleterious roles of NETs and how this knowledge may reveal new therapeutic strategies to modulate neurodegenerative diseases and preserve neural integrity, offering valuable insights for potential applications in clinical practice.},
}

@article {pmid42651138,
year = {2026},
author = {Lu, S and Chen, Z and Wang, Y and Bian, H and Yu, S and Huang, L},
title = {Brain O-GlcNAcylation in Neurodegenerative Diseases: Context-Dependent Mechanisms and Precision Therapeutic Translation.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/brainsci16080828},
pmid = {42651138},
issn = {2076-3425},
support = {LH2019H106//Natural Science Foundation of Heilongjiang Province/ ; YQJH2023152//Excellent Young Teachers Basic Research Support Program" for Provincial Undergraduate Colleges in Heilongjiang Province/ ; ZHY2025-009//Heilongjiang Province Traditional Chinese Medicine Research Project/ ; },
abstract = {O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) is a dynamic, nutrient-sensitive post-translational modification that couples hexosamine biosynthesis pathway flux to protein function in neurons and glia. This reversible cycling, catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), integrates glucose, glutamine, acetyl-CoA, and nucleotide metabolism with synaptic activity, mitochondrial adaptation, transcriptional regulation, proteostasis, and neuroimmune signaling. Dysregulated O-GlcNAc cycling has been implicated in major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Huntington's disease (HD), through effects on disease-related proteins, autophagy, mitochondrial function, and inflammatory networks. However, available evidence does not support a universal model in which global O-GlcNAc elevation is uniformly protective or global reduction is uniformly pathogenic. In this mechanistic narrative review, we integrate disease-specific and substrate-focused findings while distinguishing relatively mature translational evidence from model-based or hypothesis-generating observations. We propose a state-resolved framework in which disease-relevant O-GlcNAc states are interpreted across biological contexts, substrate/site specificity, and intervention dynamics. This framework helps reconcile divergent findings across experimental systems and highlights the limitations of indiscriminate global pathway modulation. Although OGA inhibitors represent the most advanced therapeutic strategy, their broad substrate effects underscore the need for pharmacodynamic biomarkers, human validation, brain-targeted delivery, and state-resolved approaches. Moving from bulk O-GlcNAc measurements toward precise correction of disease-relevant O-GlcNAc states across defined biological contexts will be essential for translating this biology into clinically meaningful interventions.},
}

@article {pmid42651198,
year = {2026},
author = {Harris, KE and Lascaratos, G and Chau, KY},
title = {Mitochondrial Complex V Dysfunction in Neurodegeneration: Secondary Bystander or Primary Driver?.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/brainsci16080890},
pmid = {42651198},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: Mitochondrial Complex V (Complex V [CX-V], or ATP synthase) is the terminal enzyme of oxidative phosphorylation and is responsible for the majority of cellular ATP production. An increasing body of evidence suggests that CX-V dysfunction may contribute to mitochondrial impairment observed in neurodegenerative disease. This review evaluated current research on the structure, regulation, and function of CX-V, examined the consequences of CX-V dysfunction, and assessed its proposed role in neurodegenerative disorders.

METHODS: A comprehensive review of the published literature was carried out, with emphasis on primary research investigating CX-V structure and function, inherited CX-V disorders, and experimental evidence linking CX-V dysfunction to neurodegenerative disease. The reviewed studies used a range of experimental approaches, including structural biology, biochemical studies, patient-derived cellular models, animal models and post-mortem human tissue.

RESULTS: Current evidence demonstrates that disruption of CX-V impairs ATP production, alters mitochondrial membrane potential, and oxidative phosphorylation, and that pathogenic variants cause primary mitochondrial disease. Across Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis/frontotemporal dementia, glaucoma and inherited optic neuropathies, alterations in CX-V activity, regulation and structural integrity are consistently associated with mitochondrial dysfunction. Direct evidence supporting CX-V as a primary driver of neurodegeneration remains very limited, with many observations originating from broader studies of general mitochondrial dysfunction.

CONCLUSIONS: CX-V dysfunction represents a recurring feature of mitochondrial impairment across a variety of neurodegenerative disorders and may exacerbate neuronal vulnerability by disrupting cellular bioenergetics. Current evidence indicates that CX-V may serve as a common downstream target of multiple pathological pathways rather than acting as a primary pathological factor. Future studies require direct assessment of CX-V activity in clinically relevant human models and patient tissues to determine its contribution to disease progression and examine its potential as a therapeutic target.},
}

@article {pmid42177450,
year = {2026},
author = {Ghasemi, F and Khoshnam Rad, N and Rashidinejad, B and Nasrollahzadeh, M},
title = {Pulmonary toxocariasis presenting as migratory pulmonary infiltrates and mediastinal lymphadenopathy: a case report and literature review.},
journal = {BMC pulmonary medicine},
volume = {26},
number = {1},
pages = {},
pmid = {42177450},
issn = {1471-2466},
mesh = {Humans ; Female ; Middle Aged ; *Toxocariasis/diagnosis/drug therapy/complications ; *Lymphadenopathy/parasitology ; Albendazole/therapeutic use ; Animals ; Tomography, X-Ray Computed ; Toxocara canis/isolation & purification ; Anthelmintics/therapeutic use ; *Lung Diseases, Parasitic/diagnosis/drug therapy ; *Pulmonary Eosinophilia/parasitology/diagnosis ; },
abstract = {BACKGROUND: Pulmonary toxocariasis, caused by the nematode Toxocara canis or T. cati, is an underdiagnosed cause of eosinophilic lung disease with highly variable radiological presentation that often mimics malignancy or other eosinophilic conditions.

CASE PRESENTATION: A 53-year-old female smoker presented with progressive dyspnea and cough. Initial chest CT revealed right lower lobe consolidation with mediastinal lymphadenopathy (station 4R with short-axis diameters 12 mm), raising concern for lung cancer. Bronchoscopy with EBUS-TBNA was non-diagnostic. The patient was empirically started on dexamethasone (8 mg daily, tapered over 3 months) for suspected organizing pneumonia. During steroid taper, her symptoms recurred with delayed emergence of peripheral eosinophilia (670/µL; initial absolute eosinophil count on presentation was 90/µL), elevated IgE (456 IU/mL), and serial CT scans demonstrating migratory pulmonary infiltrates involving the right lower, right middle, and left lower lobes. A history of raw beef liver consumption prompted serological testing, which confirmed Toxocara canis infection. Treatment with albendazole alone (400 mg twice daily for 14 days, without corticosteroids) resulted in complete clinical and radiological resolution.

LITERATURE REVIEW: We searched PubMed and Scopus (January 2014 - February 2026) for English- and French-language case reports of pulmonary toxocariasis. Fourteen new cases were identified and analyzed alongside the 12 cases from Ranasuriya et al.'s [1] review. These 26 cases demonstrate marked radiologic heterogeneity: multiple bilateral nodules (50%), consolidations (23%), pleural effusion (27%), and migratory infiltrates (8%). Pleural effusion has emerged as a distinct manifestation in seven recent cases. Delayed eosinophilia occurred in 12% of cases. Immunocompromised states (including primary ciliary dyskinesia, hematologic malignancies, and immunosuppressive therapy) were present in 23% of cases and may predispose to atypical presentations.

CONCLUSION: Pulmonary toxocariasis should be considered in patients with migratory infiltrates, unexplained eosinophilic pleural effusion, or lung nodules with eosinophilia. A meticulous dietary and exposure history is essential. Diagnosis is confirmed by serology, and patients respond well to albendazole therapy.},
}

Humans
Female
Middle Aged
*Toxocariasis/diagnosis/drug therapy/complications
*Lymphadenopathy/parasitology
Albendazole/therapeutic use
Animals
Tomography, X-Ray Computed
Toxocara canis/isolation & purification
Anthelmintics/therapeutic use
*Lung Diseases, Parasitic/diagnosis/drug therapy
*Pulmonary Eosinophilia/parasitology/diagnosis

@article {pmid42629129,
year = {2026},
author = {Sha, L and Jha, S},
title = {Microglia extracellular traps (MiETs) in Neurodegeneration: Mechanisms, Evidence Gaps, and Untapped Therapeutic Promise.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {307-341},
doi = {10.1016/bs.ai.2026.04.008},
pmid = {42629129},
issn = {1557-8445},
mesh = {Humans ; *Extracellular Traps/immunology/metabolism ; *Microglia/immunology/metabolism ; Animals ; *Neurodegenerative Diseases/immunology/therapy/metabolism/pathology ; Histones/metabolism ; Signal Transduction ; Neuroinflammatory Diseases/immunology ; },
abstract = {Microglia are the resident myeloid cells of the central nervous system, they play essential roles in neural tissue homeostasis, including synaptic pruning, clearance of debris and protein aggregates, and regulation of neuroinflammatory processes. In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, microglial activation and chronic glial-driven inflammation contribute substantially to neuronal dysfunction and loss. Beyond these well-characterised functions, recent evidence indicates that microglia can release chromatin-based extracellular traps (microglia extracellular traps, or MiETs), similar to the neutrophil extracellular traps (NETs) observed in peripheral immunity. Microglia ETs are induced by stimuli such as dopamine and microbial infection, dependent or independent of NADPH oxidase/ROS pathways and histone citrullination. This chapter provides a detailed examination of MiET formation, triggers, intracellular signalling, and structural components, as well as contribution to neurodegenerative pathology. Potential mechanisms include amplification of neuroinflammation via extracellular histones and proteases, disruption of the blood-brain barrier and extracellular matrix, synaptic damage, and possible facilitation of spread of misfolded protein aggregates. We situate MiET formation within the broader microglial functional repertoire (phagocytosis, cytokine production, synaptic stripping) and focus on how ET-dominant responses may compromise homeostatic or neuroprotective roles. The chapter reviews evidence from disease models, highlights key gaps and discusses translational implications. Targeting MiET formation or promoting the clearance of MiETs represents promising, yet unexplored, therapeutic avenues in neurodegenerative disease. By focusing on MiETs, this work expands the conceptual framework for microglial pathogenicity and invites future mechanistic and translational research.},
}

Humans
*Extracellular Traps/immunology/metabolism
*Microglia/immunology/metabolism
Animals
*Neurodegenerative Diseases/immunology/therapy/metabolism/pathology
Histones/metabolism
Signal Transduction
Neuroinflammatory Diseases/immunology

@article {pmid42631129,
year = {2026},
author = {Nuñez, E and Muguruza-Montero, A and Arrizabalaga-Iriondo, A and Zayas-Arrabal, J and M-Alicante, S and Urrutia, J and Revuelta, M},
title = {KV3.1 channel modulation: a systematic review of pharmacological intervention strategies.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1821275},
pmid = {42631129},
issn = {1663-9812},
abstract = {INTRODUCTION: Voltage-gated potassium channels of the KV3 subfamily, particularly KV3.1 (encoded by KCNC1), are essential regulators of fast-spiking inhibitory interneuron activity and high-frequency neuronal firing, enabling precise control of neuronal excitability and network synchrony. Growing evidence links KV3.1 dysfunction to epilepsy, schizophrenia, tinnitus, fragile X syndrome, amyotrophic lateral sclerosis, and KCNC1 related developmental and epileptic encephalopathies, positioning this channel as a promising therapeutic target.

METHODS: This systematic review, conducted in accordance with PRISMA guidelines, evaluates original studies published between 2016 and January 2026 that investigated pharmacological modulation of KV3.1 using in vitro, in vivo, structural, and translational approaches.

RESULTS: A total of thirty-two studies met the predefined PICOS criteria. The literature reveals two pharmacological strategies: positive allosteric modulation aimed at enhancing fast-spiking inhibitory interneuron function and restoring excitation inhibition balance, and state-dependent channel inhibition, particularly relevant for pathogenic gain of function KCNC1 variants.

DISCUSSION: While early positive allosteric modulators demonstrated proof of mechanism with limited clinical success, second-generation compounds exhibit improved translational potential, including evidence that they modulate functional brain networks in humans. In parallel, clinically approved antidepressants have been identified as open-channel blockers of KV3.1, enabling mutation-specific therapeutic repurposing.

CONCLUSIONS: Collectively, these findings highlight KV3.1 modulation as a context-dependent and increasingly precise pharmacological strategy for neurological and neurodevelopmental disorders.},
}

@article {pmid42632975,
year = {2026},
author = {Saeed, Y and Fatima, M and Rehman, MU and Aslam, MH},
title = {Diagnostic Delay in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis Comparing Time From Symptom Onset to Diagnosis in Bulbar-Onset Versus Limb-Onset Disease.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e113188},
pmid = {42632975},
issn = {2168-8184},
abstract = {Diagnostic delay is a recognized challenge in amyotrophic lateral sclerosis (ALS), depriving patients of timely access to disease-modifying therapy and multidisciplinary care. Although several individual cohorts have reported diagnostic delay separately for bulbar-onset and limb-onset ALS, few studies have directly compared the two, and their estimates have not been pooled. We aimed to compare time from symptom onset to diagnosis in bulbar-onset versus limb-onset ALS. We searched PubMed and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) from inception through April 2026 for studies reporting diagnostic delay separately for the two onset types. Where upper- and lower-limb onset were reported separately, these were combined into a single limb-onset group using standard formulae; medians with interquartile ranges were converted to means and standard deviations using the method of Wan et al. A random-effects meta-analysis (DerSimonian-Laird) pooled studies reporting a usable measure of dispersion by onset group, with the remaining studies summarized narratively. The outcome was the mean difference (MD) in diagnostic delay in months, where a negative value indicates faster diagnosis in bulbar onset; heterogeneity was quantified with I[2] and risk of bias with the Newcastle-Ottawa Scale. In total, 13 studies (898 bulbar-onset and 2,438 limb-onset patients from eight countries) met the inclusion criteria; nine contributed to the meta-analysis, as four reported no usable measure of dispersion and were summarized narratively. Bulbar-onset patients were diagnosed significantly faster than limb-onset patients (MD = -4.42 months; 95% confidence interval -5.73 to -3.11; p < 0.001), with moderate heterogeneity (I[2] = 56%). The direction of effect was consistent across all studies, and the pooled estimate was stable on leave-one-out analysis. The four non-pooled studies were each directionally consistent. Bulbar-onset ALS is diagnosed approximately 4 months faster than limb-onset ALS, likely because distinctive bulbar symptoms prompt earlier specialist referral whereas limb weakness is attributed to more common musculoskeletal or orthopedic conditions. Strategies raising awareness of limb-onset ALS among primary care and orthopedic physicians are warranted.},
}

@article {pmid42636890,
year = {2026},
author = {Guha, L and Malik, JA and Bose, B},
title = {Living drug carriers: Microbial and bioengineered platforms redefining precision therapeutic and immunomodulatory delivery.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115274},
doi = {10.1016/j.jconrel.2026.115274},
pmid = {42636890},
issn = {1873-4995},
abstract = {Microbial living therapeutics are a new class of drug-delivery materials that combine synthetic biology, immunomodulation, and advanced formulations to achieve controllable therapeutic effects in space and time. In the broad field of living drug-delivery systems, therapeutic platforms include engineered microorganisms, mammalian immune cells, stem cells, viral vectors, extracellular-vesicle-producing cells, and hybrid bioengineered living materials. This review focuses on engineered microbial living drug carriers, including genetically modified bacteria and probiotic platforms, because these systems uniquely integrate programmable biosensing, in situ therapeutic synthesis, adaptive immunomodulation, and controllable drug delivery within a single living chassis. Designed microbes and consortia possess other unique functions, such as microenvironment sensing, programmed control of gene expression, and long-lasting in situ manufacturing of therapeutic payloads not available with small-molecule or biologic drugs. Recent progress in microbial chassis engineering, genetic circuit design, and biocontainment has enabled fine-tuning of immune responses, metabolic pathways, and tissue-specific signaling in a wide range of diseases from cancer to autoimmune and inflammatory diseases, to metabolic and endocrine disorders, neuro-immunological conditions (e.g., amyotrophic lateral sclerosis), infectious diseases including infectious threats without existing approved vaccines (Zika virus) as well as rare genetic disorders. Advances in formulation science, including encapsulation technologies, biomaterial-microbe hybrids, and stimuli-responsive release platforms, have enabled overcoming key translation challenges concerning microbial viability, biodistribution, safety, and controlled activation in complex physiological milieus like the gut (for enteric pathogens), tumor microenvironment (for oncolytic organisms), or injured tissues (for tissue-targeting organisms). Increasing numbers of clinical-stage LBP studies are now conducted under good manufacturing practice, standardized QC, and clinical conditions, ranging from emerging PK, biodistribution, and biomarker-driven studies to those adapted to living entities. The addition of host microbiome profiling, multi-omics analysis, and computational modeling is anticipated to increase therapeutic predictability and patient stratification. Taken together, these advances position live microbial therapeutics as programmable biological medicines with the potential for adaptive, context-specific administration and warrant further clinical development and increased integration within precision medicine-informed therapeutic approaches.},
}

@article {pmid42638120,
year = {2026},
author = {Tang, L and Fan, D},
title = {Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42638120},
issn = {2047-9158},
support = {CX25YZ13//the Chinese Institutes for Medical Research, Beijing/ ; 2022YFA1303003//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/therapy ; *Precision Medicine/methods/trends ; *Neuroinflammatory Diseases/immunology/therapy ; Animals ; Immunotherapy/methods ; },
abstract = {Neuroinflammation is no longer a secondary feature of amyotrophic lateral sclerosis (ALS), but rather a disease-modifying process that actively shapes the motor neuron vulnerability from the earliest stages of pathology. Central and peripheral immune cells, including microglia, astrocytes, and infiltrating T lymphocytes, adopt context-dependent states that can be neuroprotective or neurotoxic depending on disease stage and genetic background. These states are driven by discrete molecular programs, such as cGAS-STING-mediated innate immune sensing, NLRP3 inflammasome activation, and RIPK1-dependent necroptotic signaling, which represent tractable therapeutic targets. The repeated failure of broad-spectrum immunosuppressive trials reflects a fundamental mismatch between the non-selective interventions and the mechanistically distinct immune states of diseases. Converging transcriptomic, genetic, and immunophenotypic evidence supports the existence of putative neuroimmune endotypes in ALS, though this framework remains a working hypothesis pending prospective validation in biomarker-stratified cohorts. Advances in the following three domains are needed for realizing precision immunotherapy: standardized biomarker panels (including cerebrospinal fluid chitinases and TSPO-PET) to stratify patients by inflammatory subtype; pharmacodynamic readouts to confirm target engagement before interpreting clinical outcomes; and adaptive platform trial designs capable of evaluating mechanism-matching interventions in defined subgroups. This review integrates ALS-associated neuroinflammation with emerging precision medicine strategies, arguing that the central translational question is no longer whether or not to target neuroinflammation, but how, when, and in whom neuroinflammation should be targeted.},
}

Humans
*Amyotrophic Lateral Sclerosis/immunology/therapy
*Precision Medicine/methods/trends
*Neuroinflammatory Diseases/immunology/therapy
Animals
Immunotherapy/methods

@article {pmid42640367,
year = {2026},
author = {Iacono, D and Feltis, GC},
title = {Beyond the Ribosome: The Expanding Role of the Nucleolus in Neurodegenerative Pathways.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42640367},
issn = {1559-1182},
mesh = {*Cell Nucleolus/metabolism/pathology ; Humans ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Ribosomes/metabolism ; Signal Transduction ; Aging/metabolism/pathology ; },
abstract = {The nucleolus, long defined by its canonical role in ribosome biogenesis, has emerged as a critical nexus for cellular homeostasis, stress sensing, and disease pathogenesis. This article synthesizes a broad range of evidence to construct a comprehensive model of the nucleolus in the context of aging and neurodegeneration. We begin by detailing its fundamental architecture and the intricate process of ribosome production, before exploring the paradigm-shifting discovery of its vast, non-canonical proteome, which implicates it in DNA repair, cell cycle control, and genome stability. A central theme is the nucleolus's function as a primary cellular stress sensor, which, upon disruption by genetic, metabolic, or proteotoxic insults, initiates the nucleolar stress response. We provide a detailed examination of the downstream signaling cascades, focusing on the canonical p53-MDM2 axis and the interconnected mTOR pathway, which together translate nucleolar status into decisions of cell fate, including apoptosis and cell cycle arrest. We then focus on the brain, presenting the neuropathological and morphological alterations of the nucleolus-such as atrophy, fragmentation, and changes in volume-that serve as hallmarks of normal aging and neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and C9orf72-linked ALS/FTD. We explore the deep regulatory layers of epigenetics, where DNA methylation and histone modifications of ribosomal DNA genes are dysregulated in disease, and discuss how multi-omics approaches are unraveling the complex molecular landscape of nucleolar function. Finally, we introduce the emerging concept of a gut-brain-nucleolus axis, proposing how systemic factors like the gut microbiome may influence neuronal health by triggering nucleolar stress through inflammatory and metabolic mediators. Overall, by highlighting the nucleolus as a convergence point for diverse pathogenic pathways, we frame it as a promising and druggable target for novel therapeutic strategies aimed at promoting neuronal resilience and combating neurodegenerative diseases.},
}

*Cell Nucleolus/metabolism/pathology
Humans
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Ribosomes/metabolism
Signal Transduction
Aging/metabolism/pathology

@article {pmid42621238,
year = {2026},
author = {Palakkot, S and Banik, A},
title = {Auditory Biomarkers in Neurodegenerative Disorders: A Literature Review.},
journal = {Journal of otology},
volume = {21},
number = {3},
pages = {160-166},
pmid = {42621238},
issn = {2524-1753},
abstract = {The prevalence of neurodegenerative diseases is escalating globally. However, the conventional diagnostic framework fails to identify the pathology until substantial neuronal damage occurs. The evidence from the recent literature indicates that auditory dysfunction commonly precedes motor and cognitive symptoms across multiple neurodegenerative diseases. The pathophysiology involves both the peripheral and cortical auditory structures, which produce distinctive patterns reflects systemic neurodegeneration. Hence, this suggests auditory assessment as a valuable tool for early identification of neural degeneration. This review synthesises the contemporary literature on auditory dysfunctions and underlying pathophysiology in Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, Amyotrophic lateral sclerosis, etc. The analysis included the temporal trajectories of auditory impairment, subjective-objective measurements, and evaluated the importance of early identification and longitudinal tracking. Objective measures of central auditory processing, including Auditory Brainstem Responses, P300, Mismatch Negativity, and speech-in-noise testing, provide objective, non-invasive diagnostic tools and its sensitivity comparable to established biomarkers. Integration of standardised auditory assessment batteries into clinical protocols could enable the early identification of pathology, differential diagnosis and the development of novel therapeutic strategies for both auditory and cognitive deficits. Current review suggests that future longitudinal studies with neurodegenerative conditions should focus on the clinical utility of auditory, cognitive, and neuroimaging biomarkers and facilitate clinical translation of these findings.},
}

@article {pmid42625715,
year = {2026},
author = {Chen, D and Shen, T and Ren, H and Qiu, P},
title = {Amyotrophic lateral sclerosis and degenerative cervical myelopathy: phenotype-based diagnostic pitfalls, investigative mismatch, and practical clinical reasoning.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1901811},
pmid = {42625715},
issn = {1664-2295},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/diagnostic imaging ; Diagnosis, Differential ; Phenotype ; Magnetic Resonance Imaging ; *Spinal Cord Diseases/diagnosis/physiopathology ; *Spinal Cord Compression/diagnosis/physiopathology ; },
abstract = {Differentiating amyotrophic lateral sclerosis (ALS) from degenerative cervical myelopathy (DCM) remains difficult because the two disorders can converge clinically while diverging biologically. ALS is a progressive motor neuron disease, whereas DCM is a potentially treatable compressive myelopathy; however, both may present with upper-limb weakness, hand wasting, hyperreflexia, gait disturbance, and cervical MRI abnormalities. This narrative review examines ALS-DCM overlap through the concept of explanatory sufficiency: whether the available clinical, imaging, and electrophysiological evidence adequately explains the whole syndrome rather than a single visible abnormality. We synthesize evidence on phenotype-specific overlap, MRI-clinical mismatch, EMG/NCS distribution, somatosensory and motor evoked potentials, Gold Coast diagnostic criteria, primary lateral sclerosis, and coexistence of motor neuron disease with structural cervical pathology. The review emphasizes that MRI is indispensable but not self-interpreting, EMG/NCS is most useful when interpreted by distribution rather than positivity alone, and SEPs/MEPs can add a functional cord-conduction layer when MRI and examination are discordant. We also provide action-oriented clinical warning signs for common overlap scenarios. Rather than offering a rigid algorithm, this review proposes a clinically driven reasoning framework that helps distinguish ALS, DCM, radiculopathy, and coexistence while reducing premature diagnostic closure in neuro-spine practice.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/diagnostic imaging
Diagnosis, Differential
Phenotype
Magnetic Resonance Imaging
*Spinal Cord Diseases/diagnosis/physiopathology
*Spinal Cord Compression/diagnosis/physiopathology

@article {pmid42619255,
year = {2026},
author = {Gadhave, DG and Jadhav, AB and Waghamode, NB and Khot, S and Khan, R and Hole, R and Dhobale, SM and Aswar, M and Paudel, KR},
title = {Mitochondria-Targeted Nanotherapies in Aging Neurodegenerative Disorders: Emerging Prospects and Clinical Potential.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e71594},
doi = {10.1002/adhm.71594},
pmid = {42619255},
issn = {2192-2659},
abstract = {Aging is a significant risk factor of neurodegenerative disorders (NDs) such as Huntington's, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Although several clinical, neuroimaging, and biomarker-based diagnostic approaches are available for NDs, their limited sensitivity for early-stage detection, disease specificity, and prediction of disease progression continue to present significant clinical challenges, often resulting in delayed diagnosis and therapeutic intervention. According to previously published works, the preliminary pathological feature of such disorders is mitochondrial dysfunction. This may lead to elevated oxidative stress, impaired mitophagy, unbalanced mitochondrial function, and bioenergetic failure. This review examines how mitochondria-targeted nanotherapeutic approaches can overcome these pathological barriers and improve therapeutic outcomes in aging-associated neurodegeneration. Targeted delivery of drug-loaded nanocarriers, such as gene-delivery, lipid-based, metallic, and polymeric nanoparticles, has emerged as a potential platform to deliver medication directly to defective mitochondria. It may increase mitochondrial biogenesis, maintain redox balance, and protect against neuronal degeneration. This work incorporates disease-specific mitochondrial pathology with current progress in targeted nanotherapeutics, age-associated delivery barriers, clinical revolution, and emerging artificial intelligence (AI)-enabled precision therapeutic approaches. Mitochondria-targeted nanotherapeutics depict a potential disease-modifying strategy for aging-related NDs. However, further advancements in targeting efficacy, scalable production, long-term safety, and clinical validation can facilitate a successful clinical revolution.},
}

@article {pmid42552132,
year = {2026},
author = {Labrèche, F and Prud'homme, P and Gagnon, M and Dupré, N and Gravel, S},
title = {Occupational exposure to pesticides increases the risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Occupational and environmental medicine},
volume = {83},
number = {5},
pages = {291-300},
doi = {10.1136/oemed-2025-110662},
pmid = {42552132},
issn = {1470-7926},
mesh = {Humans ; *Occupational Exposure/adverse effects ; *Amyotrophic Lateral Sclerosis/chemically induced/epidemiology ; *Pesticides/adverse effects/toxicity ; Risk Factors ; *Occupational Diseases/chemically induced ; Female ; },
abstract = {OBJECTIVE: To systematically review the evidence on the association between occupational exposure to pesticides and the risk of amyotrophic lateral sclerosis (ALS).

METHODS: A systematic search, conducted in eight bibliographic databases for publications between 1990 and 2025, identified observational studies estimating the risk of ALS after occupational pesticide exposure. Study quality was assessed using the WHO Risk of Bias (RoB) assessment instrument for systematic reviews, with the ROBINS-E (RoB in non-randomised studies of exposure) tool domains of bias. Pooled risk estimates were produced using random-effects models with restricted maximum likelihood, heterogeneity was assessed with I² statistics, and meta-regressions and publication bias explored with funnel plots and Egger's test.

RESULTS: Eight case-control studies (1734 cases) were retained for meta-analysis from 767 initially screened articles. 'Ever' occupational exposure to pesticides was associated with an increased risk of ALS (n=6 studies, pooled OR (pOR)=1.6; 95% CI 1.1, 2.2; I²=57%), for combined sexes. The risk for exposure to herbicides was slightly greater (pOR=1.7, I[2]=0.0%) than for exposure to insecticides or fungicides (pORs=1.6, I[2]=0.0%). Based on three studies, ever exposure to high levels of pesticides was associated with a higher risk (pOR=2.7; 95% CI=1.4, 5.0) than exposure to low levels (pOR=1.9; 95% CI=1.0, 3.7). Self-reported exposure assessment methods and older publication dates (<2015) were statistically significant predictors of the effect size.

CONCLUSION: Despite the small number of studies and some heterogeneity, our results add to the evidence suggesting that occupational exposure to pesticides may increase the risk of ALS.},
}

Humans
*Occupational Exposure/adverse effects
*Amyotrophic Lateral Sclerosis/chemically induced/epidemiology
*Pesticides/adverse effects/toxicity
Risk Factors
*Occupational Diseases/chemically induced
Female

@article {pmid42618940,
year = {2026},
author = {Saka, AK and Godhwani, K and Ramasamy, V and Soh, BL and Lingam, M and Lofters, A and Gerstle, D and Selby, P and LeBlanc, A and Pritlove, C and Sayani, A},
title = {The use of deliberative dialogue in health services research: a scoping review.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {},
pmid = {42618940},
issn = {2056-7529},
support = {TLP - 185094/CAPMC/CIHR/Canada ; },
abstract = {INTRODUCTION: Deliberative Dialogue (DD) is a structured participatory approach that brings together research evidence, professional expertise, and lived/living experience to support informed discussion and decision-making in health research. DD is increasingly used in the co-design, co-implementation, and co-evaluation of health-promoting interventions, where decisions must be both evidence-informed and responsive to local contexts, priorities, and needs. However, published studies vary considerably in how DD is described and reported, particularly in relation to facilitation, evidence use, participant preparation, power dynamics, and follow-up. This scoping review examined the application of DD in health services research, focusing on its methodological processes, reported outcomes and challenges, engagement of different interest-holders, and the rationales underlying its use.

METHODS: A scoping review was conducted following Arksey and O'Malley's framework and reported in accordance with PRISMA-ScR guidelines. Searches of OVID Medline, PsycINFO, PubMed, CINAHL, and Scopus identified 1,793 records. After screening and consolidating duplicate reports, 15 unique studies met the inclusion criteria. Data were extracted using a template informed by the Guidance for Reporting Involvement of Patients and the Public (GRIPP2), the Consolidated Standards of Reporting Trials (CONSORT), and Boyko et al.'s model of DD. The review was conducted using a critical Patient-Oriented Research (cPOR) approach, which centres lived/living experience, promotes shared decision-making between patient partners and researchers, and attends to the influence of power and structural contexts on knowledge production. The interdisciplinary team, including patient partners, researchers, clinicians, policymakers, and decision-makers, co-developed the study, contributed to data interpretation, and collaboratively refined the findings through iterative and reflexive discussion.

FINDINGS: The 15 included studies were published between 2012 and 2024 and represented diverse geographic and health-system contexts. DD was used to support intervention co-design, implementation planning, evaluation, priority-setting, guideline development, and service improvement. Studies consistently reported the involvement of multiple interest-holder groups and the development of practical outputs, including curricula, decision aids, care models, action plans, guidelines, and priority-setting frameworks. However, reporting of methodological processes was inconsistent. Only a minority of studies described facilitation protocols, participant preparation, strategies to address power dynamics, accessibility supports, or follow-up activities. While DD was associated with enhanced trust, mutual understanding, contextual relevance, and collaborative decision-making, evidence of longer-term impacts was limited. The synthesis also revealed substantial variation in how studies reported participant engagement, evidence use, consensus-building processes, and the translation of deliberative outputs into intervention-related decisions.

This review highlights DD as a valuable approach for collaborative, evidence-informed, and context-sensitive health services research. Across the included studies, DD was used to bring together diverse forms of knowledge and generate practical outputs to support intervention development and improvement. However, methodological details related to facilitation, accessibility, participant support, management of power dynamics, decision-making processes, and longer-term impacts were often underreported. These gaps point to the need for more transparent and equity-oriented reporting of DD, particularly in relation to how people with lived/living experience are engaged and how their contributions influence intervention-related decisions. Strengthening reporting in these areas may improve the transparency, reproducibility, and accountability of DD in the co-design, co-implementation, and co-evaluation of health interventions.},
}

@article {pmid42618698,
year = {2026},
author = {Shrestha, N and Munn, Z and Calma, A and Pavey, N and Tsuji, Y and Menon, P and Padovani, A and Risi, B and Ferullo, L and Filosto, M and Jewett, G and Shibuya, K and Otani, R and Shimizu, T and Kuwabara, S and Noto, YI and Kitaoji, T and Johnsen, B and Shen, D and Cui, L and van den Berg, LH and van Eijk, RPA and van Damme, P and Kiernan, MC and Giles, L and Vucic, S},
title = {Gold Coast criteria for ALS diagnosis: individual participant data meta-analysis.},
journal = {Journal of neurology},
volume = {273},
number = {9},
pages = {},
pmid = {42618698},
issn = {1432-1459},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Humans ; Sensitivity and Specificity ; },
abstract = {BACKGROUND: To evaluate the diagnostic accuracy of the Gold Coast criteria (GCC) and compare their performance with the revised El Escorial (rEEC) and Awaji criteria in patients with suspected amyotrophic lateral sclerosis (ALS).

METHODS: Embase, MEDLINE, and Scopus were searched for English-language studies published between January 1, 2020, and August 11, 2025. Eligible studies assessed the diagnostic accuracy of GCC compared with rEEC and Awaji criteria in suspected ALS. Authors were invited to contribute individual participant data. Data were checked, harmonised, and recoded. A one-stage individual-participant data meta-analysis, adjusted for age and sex, was performed. Diagnostic performance was assessed using pooled sensitivity, specificity, and area under the receiver operating characteristic curve. Risk of bias was assessed using QUADAS-2 and QUADAS-C, and certainty of evidence using GRADE for diagnostic test accuracy. The study was registered with PROSPERO, CRD420251123597.

RESULTS: Individual participant data were available for 3007 participants from five international studies. GCC demonstrated higher sensitivity than rEEC and Awaji criteria: 0.96 (95% confidence interval [CI] 0.93-0.98) versus 0.87 (95% CI 0.78-0.92) and 0.87 (95% CI 0.78-0.93), respectively. Certainty of evidence for sensitivity was moderate at pre-test probabilities of 50% and 75%, and low at 25%. Specificity was numerically lower for GCC at 0.68 (95% CI 0.53-0.81) compared with rEEC at 0.73 (95% CI 0.59-0.83) and the Awaji criteria at 0.72 (95% CI 0.57-0.83). The certainty of evidence for specificity was rated as very low across all assessed pre-test probabilities (25%, 50%, and 75%).

CONCLUSIONS: GCC provide a sensitive framework for suspected ALS and may support earlier diagnosis in specialist settings. Specificity was imprecise and heterogeneous, supporting use with mimic exclusion and longitudinal reassessment.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Humans
Sensitivity and Specificity

@article {pmid42149647,
year = {2026},
author = {Hui, LM and Yu, E and Chung, A and Kwan, BYM},
title = {Artificial intelligence for assessment in competency-based medical education: current practices and future directions.},
journal = {Postgraduate medical journal},
volume = {102},
number = {1211},
pages = {806-816},
doi = {10.1093/postmj/qgaf195},
pmid = {42149647},
issn = {1469-0756},
mesh = {*Competency-Based Education/methods/trends ; Humans ; *Artificial Intelligence ; *Clinical Competence/standards ; *Educational Measurement/methods ; },
abstract = {BACKGROUND: Competency-Based Medical Education (CBME) relies on frequent, competency-focused assessments, which can be challenging to implement consistently. Artificial Intelligence (AI) holds promise to improve assessment efficiency, objectivity, and feedback in CBME, but its use remains in early stages with limited understanding of current practices and evaluation methods. This study aims to map existing AI applications in CBME assessments to guide future work.

METHODS: A comprehensive search was performed in MEDLINE (Ovid), EMBASE (Ovid), PsycINFO, and Scopus using tailored keywords and MeSH terms. Included studies focused on the deployment of AI for assessment within CBME, covering applications in generating, analyzing, or interpreting evaluation data across undergraduate, graduate, and continuing professional education. The PRISMA-ScR guidelines were used to ensure transparent reporting, and findings were synthesized following Levac et al.'s approach.

RESULTS: Of the 1002 search results, 32 studies met the inclusion criteria. Key findings indicate a wide application of AI from surgical or procedural skill assessment, to clinical note assessment, communication assessment, feedback generation, projected trainee performance, and analysis of narrative feedback from supervisors.

CONCLUSION: This review highlights potential advantages, such as timely evaluations, and challenges, such as lack of granularity, of AI integration. In conclusion, thoughtful integration of AI into competency-based medical education can complement traditional assessment methods and enhance learner outcomes, provided it is supported by robust infrastructure, ethical oversight, and collaborative policy development.},
}

*Competency-Based Education/methods/trends
Humans
*Artificial Intelligence
*Clinical Competence/standards
*Educational Measurement/methods

@article {pmid42614249,
year = {2026},
author = {Sheppard, B and Durnell, L and Haufler, AJ},
title = {From emergence to amplification: an analysis of lifecycle models to address health mis-disinformation in the digital environment.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1814102},
pmid = {42614249},
issn = {2296-858X},
abstract = {Health misinformation and disinformation (mis-disinformation) on social media presents a growing threat to individual and population health, societal resilience, and national security. While social media enables the rapid dissemination of health information, it also facilitates the spread of health mis-disinformation, a challenge further compounded by foreign influence campaigns, AI-generated content, and divergent regulatory environments. Effective interventions require tailoring to local socio-cultural and geo-political contexts. This article proposes a lifecycle model for health professionals that conceptualizes how content creation, dissemination, exposure, belief formation, and behavioral outcomes interact and can be targeted through strategic interventions to improve health outcomes and mitigate adverse behavioral effects. To achieve this, the article characterizes the challenges posed by the current and emerging health information environment; identifies and evaluates mis-disinformation lifecycle models in order to strengthen the existing knowledge base; and assesses the current state of knowledge and gaps on comparing intervention strategies to elicit desired behavioral responses, with an emphasis on individual approaches (e.g., debunking, media literacy, fact checking). A review of literature (2020-2025) identified 13 cross-comparative intervention studies which focused on key findings. Four lifecycle models were identified and assessed against six criteria derived from the lifecycle literature to identify the most suitable framework for adaptation in the public health domain. Kruijver et al.'s C5 Interaction Model emerged as the framework that satisfied the greatest number of criteria and was selected for adaptation. The model was extended to account for diverse socio-political and information environments, emerging technological interventions, and the distinct challenges posed by both mis-disinformation. Adaptation involved integrating concepts from risk perception, the Social Amplification of Risk Framework, and Social Judgment Theory, alongside health-specific examples to enhance relevance and practical applicability. To help translate the insights gained to strategy, we also convey the information in an Integrated Framework for Managing Health Mis-disinformation. By linking the evolution of health mis-disinformation to targeted interventions, the model and framework provide a foundation for promoting healthier behaviors and mitigating the adverse effects of misleading health information across diverse socio-demographic and cultural settings to improve health outcomes.},
}

@article {pmid42617572,
year = {2026},
author = {Tang, WX and Yang, C and Zhang, M and Kushida, CA and de Lecea, L and Li, SB},
title = {Sleep-wake control with age and neurodegenerative diseases.},
journal = {Sleep medicine reviews},
volume = {90},
number = {},
pages = {102352},
doi = {10.1016/j.smrv.2026.102352},
pmid = {42617572},
issn = {1532-2955},
abstract = {Aging causes dramatic alterations in bodily functions. Among them, sleep quality declines with age, particularly in individuals with neurodegenerative diseases. In this review, we first describe alterations in sleep-wake architecture and discuss potential mechanisms underlying sleep disorders that arise with age. We discuss evidence linking sleep disorders with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) syndrome. Even though the causes of AD, PD, PSP, and HD are diverse, several shared symptoms including difficulty falling asleep, fragmented sleep, and disrupted circadian rhythm collectively suggest their pathologies disrupt sleep-wake control. Hyperexcitability of implicated neurons is commonly observed prior to neurodegeneration. Upregulated neuronal excitability in the early phase of these diseases appears as a potential shared mechanism among neurodegenerative diseases. Abnormal protein accumulation and aggregation in these diseases exacerbate neuronal circuit hyperactivity by increasing neurons' intrinsic excitability or dampening inhibitory inputs to neurons controlling sleep-wake cycles. A better understanding of the mechanisms underlying sleep disorders that emerge with age may greatly benefit the development of novel preventative and therapeutic strategies for neurodegenerative diseases, and therefore improve the life quality of older adults.},
}

@article {pmid42612795,
year = {2026},
author = {Li, J and Duan, H and Hao, P and Zhao, W and Gao, Y and Yang, Z and Li, X},
title = {Regenerative medicine for neurodegenerative diseases:History, Strategies, and Clinical Advances.},
journal = {Translational research : the journal of laboratory and clinical medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.trsl.2026.08.005},
pmid = {42612795},
issn = {1878-1810},
abstract = {In the context of global ageing, the prevalence of neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), is rapidly increasing. However, current symptomatic treatments have achieved limited benefits in clinical settings and fundamentally fail to reverse the progressive loss of specific neuronal populations. Halting neurodegeneration and restoring impaired cognitive, motor or visual functions through nerve regeneration and circuit reconstruction represent the clinically meaningful goals for treatments of NDDs. Regenerative medicine has emerged as a promising paradigm to address this unmet need. In this review, we trace the historical evolution of regenerative therapies for NDDs - from early exploratory cell transplantation to modern approaches involving pluripotent stem cells (PSCs) and in vivo direct reprogramming. Furthermore, we elucidate the core strategies of regenerative medicine within an integrated framework encompassing "Replacement", "Regeneration", and "Rejuvenation". Finally, we highlight recent advances in clinical research, particularly milestone trials in cell replacement therapy for PD, as well as the application of mesenchymal stem cells (MSCs) in AD and ALS.},
}

@article {pmid42613144,
year = {2026},
author = {Valverde, A and Blasco, H and Corcia, P and Herault, O and Magistretti, P and Herault, L and Cali, C and Bartesaghi, L and Stone, J and Mitrofanis, J},
title = {Exploring the effect of red and near-infrared light on neurodegenerative disease: A focus on amyotrophic lateral sclerosis, Charcot's devastating disease of the motor system.},
journal = {International review of neurobiology},
volume = {189},
number = {},
pages = {205-236},
doi = {10.1016/bs.irn.2026.01.013},
pmid = {42613144},
issn = {2162-5514},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/radiotherapy ; Animals ; *Infrared Rays/therapeutic use ; Red Light ; *Neurodegenerative Diseases/therapy ; },
abstract = {All neurodegenerative diseases, from Alzheimer's disease to amyotrophic lateral sclerosis (ALS), are characterised by a relentless and progressive degeneration of neurones. The degenerating neurones suffer from mitochondrial dysfunction, glutamate excitotoxicity, metabolic disorder and atypical protein aggregations; there is also widespread neuroinflammation and damage to the neurovascular unit across the nervous system. Unfortunately, there is no current treatment option that addresses all, if not many, of these striking abnormalities, one that stops or even slows the progression of the disease (ie neuroprotective). In this chapter, we explore the potential effectiveness of red and near infrared light (R-NIr) on ALS, one of the most devastating of all the neurodegenerative diseases. This condition impacts the motor system, from the cerebral cortex and brainstem to the spinal cord, as well as many skeletal muscles. Individuals suffer greatly and the survival period after onset of the first signs is often very short, averaging just over 2 years, as against 4-8 years in dementia. We outline two main reasons why R-NIr may have positive outcomes in ALS; (1) R-NIr has been shown to be neuroprotective in many other neurodegenerative diseases, improving cell function and survival, and; (2) unlike many other treatments attempted previously, R-NIr addresses many, if not all features of pathology associated with ALS. In summary, we suggest that R-NIr, with its multi-modal effect, could be a valuable treatment option for patients with ALS, particularly if the treatment is started early, before the development of excessive cellular damage.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/radiotherapy
Animals
*Infrared Rays/therapeutic use
Red Light
*Neurodegenerative Diseases/therapy

@article {pmid42613627,
year = {2026},
author = {Jamali, MC and Shafie, A and Alqahtani, AJ and Al-Samawi, RI and Alyami, HM and Ashour, AA and Felemban, MF and Mansuri, N and Tayeb, FJ and Ahmad, I and Mudhafar, M and Sheweita, SA},
title = {Advances in the clinical application of mesenchymal stem cells for neurological disorders.},
journal = {Stem cell research & therapy},
volume = {17},
number = {1},
pages = {},
pmid = {42613627},
issn = {1757-6512},
mesh = {Humans ; *Mesenchymal Stem Cell Transplantation/methods ; *Mesenchymal Stem Cells/cytology/metabolism ; *Nervous System Diseases/therapy/pathology ; Animals ; Amyotrophic Lateral Sclerosis/therapy/pathology ; Alzheimer Disease/therapy/pathology ; },
abstract = {Therapeutic approaches employing mesenchymal stem cells (MSCs) have emerged as a promising avenue for investigating treatments for neurological disorders. This strategy aims to capitalize on the biological properties of MSCs to support the repair of damaged neural tissue and modulate pathological processes. This review provides a comprehensive overview of the current clinical evidence regarding MSC applications in major neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other pertinent disorders. Across clinical studies, MSC administration has generally demonstrated a favorable safety profile and procedural feasibility. However, therapeutic efficacy remains variable and inconsistent across trials. Importantly, differences in MSC sources, manufacturing procedures, delivery routes, dosing strategies, and patient selection contribute substantially to the heterogeneity of reported outcomes. Therefore, the current body of evidence supports the safety of MSC-based interventions, but their clinical effectiveness has not yet been consistently demonstrated. Future progress will depend largely on the standardization of cell preparation and treatment protocols, improved biomarker-driven patient stratification, and rigorously designed large-scale randomized trials.},
}

Humans
*Mesenchymal Stem Cell Transplantation/methods
*Mesenchymal Stem Cells/cytology/metabolism
*Nervous System Diseases/therapy/pathology
Animals
Amyotrophic Lateral Sclerosis/therapy/pathology
Alzheimer Disease/therapy/pathology

@article {pmid42613642,
year = {2026},
author = {Wang, JDJ and Teo, AYT and Xiao, B and Chao, Y and Zhou, ZD and Tan, BJ and Chan, LL and Rosalie, E and Tan, EK},
title = {PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42613642},
issn = {2047-9158},
support = {LCG//National Medical Research Council/ ; STaR//National Medical Research Council/ ; },
mesh = {Humans ; *PCSK9 Inhibitors ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Proprotein Convertase 9/metabolism/genetics ; Animals ; },
abstract = {Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in hepatic cholesterol metabolism via low density lipoprotein receptor degradation. PCSK9 inhibitors have revolutionized lipid-lowering therapy, providing robust reduction of cardiovascular risk. Large-scale randomized controlled trials and long-term extensions (e.g., FOURIER and EBBINGHAUS trials) have shown no significant adverse effects of PCSK9 inhibitors on neuropsychological testing or patient-reported cognitive outcomes, even with prolonged and intensive lowering of low-density lipoproteins. Pre-clinical studies also suggest PCSK9 as a key regulator of neurobiological processes, including synaptic plasticity, amyloid-beta clearance, neuroinflammation, and blood-brain barrier integrity. Human genetic studies revealed complex, sometimes conflicting associations between PCSK9 variants and risk of Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. In this review, we highlight the pathophysiologic mechanisms, emerging experimental therapeutics and clinical implications of PCSK9 inhibition in neurodegenerative disorders. Long-term adequately powered trials with robust neuropsychological, biomarker, and imaging endpoints, as well as mechanistic studies in human-derived models are needed to establish the cardiovascular and neurocognitive implications of PCSK9 inhibition and guide precision medicine strategies for those at elevated risk of neurodegeneration.},
}

Humans
*PCSK9 Inhibitors
*Neurodegenerative Diseases/drug therapy/metabolism
*Proprotein Convertase 9/metabolism/genetics
Animals

@article {pmid41997149,
year = {2026},
author = {Wu, T and Yuan, L and Sasaki, Y and Chen, SJ and Buchser, W and Bloom, AJ and DiAntonio, A and Milbrandt, J},
title = {SARM1 executes neuronal parthanatos and promotes excitotoxic cell death.},
journal = {Neuron},
volume = {114},
number = {16},
pages = {2975-2986.e5},
pmid = {41997149},
issn = {1097-4199},
support = {R01 NS065053/NS/NINDS NIH HHS/United States ; R01 NS087632/NS/NINDS NIH HHS/United States ; R01 NS133348/NS/NINDS NIH HHS/United States ; },
mesh = {*Armadillo Domain Proteins/metabolism ; Animals ; Humans ; *Cytoskeletal Proteins/metabolism ; *Cell Death/physiology/drug effects ; *Parthanatos/physiology ; *Neurons/metabolism ; DNA Damage ; },
abstract = {The nicotinamide adenine dinucleotide (NAD[+]) hydrolase sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is the central executioner of pathological axon degeneration and is allosterically activated by an increased nicotinamide mononucleotide (NMN)/NAD[+] ratio. DNA damage induces NAD[+] loss and an increased NMN/NAD[+] ratio by hyperactivating poly(ADP-ribose) polymerase 1 (PARP1), which triggers the parthanatos cell death pathway. Multiple mechanistically distinct DNA-damaging agents activate SARM1 and induce axon degeneration following PARP1 activation. Remarkably, SARM1 is required for key steps downstream of hyperactivated PARP1, which are pathognomonic of parthanatos, including mitochondrial depolarization, nuclear translocation of apoptosis-inducing factor (AIF), and cell death. Hence, SARM1 is an essential component of neuronal parthanatos. Moreover, complex neurodegenerative stimuli whose mechanisms include activation of parthanatos, such as 1-methyl-4-phenyl-pyridinium (MPP[+]) dopaminergic neuron toxicity and N-methyl-D-aspartate (NMDA) excitotoxicity, are potently protected by SARM1 inhibition. These findings place SARM1 at the nexus of multiple mechanisms driving neuronal cell death, thereby greatly expanding the potential clinical utility of SARM1 inhibitors beyond diseases of axon loss.},
}

*Armadillo Domain Proteins/metabolism
Animals
Humans
*Cytoskeletal Proteins/metabolism
*Cell Death/physiology/drug effects
*Parthanatos/physiology
*Neurons/metabolism
DNA Damage

@article {pmid42031611,
year = {2026},
author = {Etik, DÖ and Dişibeyaz, S and Özmert, EH},
title = {Pancreatitis due to afferent loop syndrome: A case report and a brief review of the literature.},
journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology},
volume = {27},
number = {3},
pages = {438-442},
doi = {10.1016/j.ajg.2026.02.003},
pmid = {42031611},
issn = {2090-2387},
mesh = {Humans ; Male ; *Afferent Loop Syndrome/complications/diagnosis ; Adult ; *Pancreatitis/etiology/diagnosis/therapy ; Gastric Bypass/adverse effects ; Gastrectomy/adverse effects ; Abdominal Pain/etiology ; Diagnosis, Differential ; },
abstract = {Afferent loop syndrome (ALS) should be a part of the differential diagnosis in a patient with acute pancreatitis with a history of gastric surgery. Although it is a rare clinical entity, association of ALS with acute pancreatitis can lead to poor clinical outcomes. Herein, we report the case of a 41-year-old man with a history of subtotal gastrectomy and Roux-en-Y gastric bypass who presented with abdominal pain and tenderness. Treatment of choice in this case was purely medical. A brief review of similar cases in the literature highlights the wide array of etiologies of acute pancreatitis due to ALS and reveals a broad spectrum of treatment options from medical to surgical.},
}

Humans
Male
*Afferent Loop Syndrome/complications/diagnosis
Adult
*Pancreatitis/etiology/diagnosis/therapy
Gastric Bypass/adverse effects
Gastrectomy/adverse effects
Abdominal Pain/etiology
Diagnosis, Differential

@article {pmid42606797,
year = {2026},
author = {Raghunathan, T and Parthasarathy, B and Prabhu, P and Mahesh, P and Dhanushkodi, A},
title = {Regenerative strategies for ALS: stem cells and extracellular vesicles.},
journal = {Discover nano},
volume = {21},
number = {1},
pages = {},
pmid = {42606797},
issn = {2731-9229},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is caused by progressive degeneration of upper and lower motor neurons. The disease is late onset, and to date, no early diagnosis is possible. Patients with ALS have a 5-year survival rate since diagnosis. Though recent studies highlighted the possible mechanisms of motor neuron degeneration in ALS, the treatment options are extremely limited. This underscores the urgent need to develop effective therapeutic strategies that can prolong patient survival and ultimately slow/halt ALS progression. Extracellular vesicles released from the degenerative milieu contribute to ALS propagation and progression by shuttling misfolded proteins, proinflammatory cytokines, and neurotoxins; thus, they could serve as a biomarker for diagnosis and prognosis. The advancement of stem cell-based therapies for neurodegenerative diseases and the evolving understanding of extracellular vesicles as potential biotherapeutics provide a ray of hope for millions of patients suffering from neurological disorders/neurodegenerative diseases like ALS.},
}

@article {pmid42609140,
year = {2026},
author = {Wedgwood, HE and Tuxworth, RI and Ahmed, Z},
title = {Exploring Genetic Therapies Targeting Amyotrophic Lateral Sclerosis in Animal Models: A Systematic Review and Meta-Analysis.},
journal = {The journal of gene medicine},
volume = {28},
number = {8},
pages = {e70106},
pmid = {42609140},
issn = {1521-2254},
support = {//LifeArc/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Animals ; Disease Models, Animal ; *Genetic Therapy/methods ; Humans ; Motor Neurons/pathology/metabolism ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disease, for which there is currently no known cure. ALS primarily affects motor neurons, with rapid deterioration, meaning symptoms develop quickly, from problems with speech and muscle weakness to breathing issues and paralysis. This systematic review aimed to explore the preclinical efficacy of various genetic therapies used to target ALS using in vivo rodent models.

METHODS: In vivo studies of genetic therapies targeting ALS and its symptoms published between January 2015 and December 2025 were included in this review. The following databases were used: Web of Science, Scopus and PubMed. The primary outcome investigated was the total number of motor neurons, with secondary outcomes of rodent survival and muscle function by observing rotarod performance also being analysed. The SYRCLE tool was used to assess risk of bias in included studies.

RESULTS: Of the 451 studies identified by searching the databases, 53 studies were found to be eligible for this systematic review. The articles were divided into subcategories depending on the gene target of each therapy. Meta-analysis of outcomes within appropriate studies showed significant improvements for the majority of selected outcomes (p < 0.05), favouring genetic therapy intervention.

CONCLUSIONS: Results suggest that genetic therapies in rodent models targeting ALS are effective. However, due to a high risk of bias in preclinical studies, further high-quality studies are warranted to support this conclusion and onward translation into the clinic.},
}

*Amyotrophic Lateral Sclerosis/therapy/genetics
Animals
Disease Models, Animal
*Genetic Therapy/methods
Humans
Motor Neurons/pathology/metabolism

@article {pmid42609516,
year = {2026},
author = {Li, T and Zhang, Q and Wu, Y and Huang, R},
title = {Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.},
journal = {MedComm},
volume = {7},
number = {9},
pages = {e70915},
pmid = {42609516},
issn = {2688-2663},
abstract = {Neurodegenerative diseases (NDs) are marked by selective neuronal vulnerability and progressive failure of neural circuits. Increasing evidence indicates that neuronal loss is not driven by a single terminal event, but emerges from interacting regulated cell death (RCD) programs. These programs are closely coupled to mitochondrial injury, proteostatic collapse, lysosomal stress, metabolic imbalance, glial state transitions, and chronic neuroinflammation. Yet, how distinct death pathways are organized across cell types, disease stages, and disease-specific microenvironments remains unresolved. This review examines RCD as an integrated pathogenic network in major NDs. Caspase and B-cell lymphoma 2 (BCL2) family signaling, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein activation, NOD-like receptor family pyrin domain containing 3 and gasdermin signaling, GPX4-linked lipid peroxidation control, and autophagy lysosomal failure are discussed as convergent stress response modules rather than isolated pathways. Across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, these modules shape neuronal fate through disease-specific interactions with mitochondrial dysfunction, iron dyshomeostasis, inflammasome activation, and microglial metabolic remodeling. We further evaluate emerging therapeutic strategies that target cell death crosstalk, restore autophagy lysosomal competence, or improve delivery to the central nervous system, highlighting the importance of molecular selectivity, cellular context, disease stage, and translational feasibility.},
}

@article {pmid42610209,
year = {2026},
author = {Lv, C and Zhu, W and Wen, X and Da, Y},
title = {Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.},
journal = {ASN neuro},
volume = {18},
number = {1},
pages = {2715625},
pmid = {42610209},
issn = {1759-0914},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/pathology/therapy ; Animals ; *Neuroinflammatory Diseases/immunology/pathology/therapy ; Disease Progression ; Blood-Brain Barrier ; Inflammation ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex and heterogeneous pathogenesis. Accumulating preclinical and clinical evidence indicates that neuroinflammation is an important modulator of ALS pathophysiology, involving activation of resident central nervous system immune cells, dysfunction of glial support systems, disruption of neurovascular barriers, and altered recruitment of peripheral immune cells. ALS-associated neuroinflammation is temporally dynamic and varies across anatomical compartments and cellular contexts. Multiple animal models, human neuroimaging, and post-mortem tissue suggest that relatively regulated or compensatory immune responses during early stage may progressively shift to persistent, maladaptive, and potentially neurotoxic inflammatory circuits in later stage. Although previous studies have described stage-dependent changes in individual immune cell populations, an integrated stage-dependent systematic framework that unifies dynamic alterations in both central and peripheral immune compartments remains insufficiently established. In this review, we propose a four-phase conceptual framework for ALS neuroinflammation across the progressive ALS pathogenesis, aiming to provide theoretical guidance for staging inflammatory therapeutic interventions.},
}

Humans
*Amyotrophic Lateral Sclerosis/immunology/pathology/therapy
Animals
*Neuroinflammatory Diseases/immunology/pathology/therapy
Disease Progression
Blood-Brain Barrier
Inflammation

@article {pmid42598001,
year = {2026},
author = {Tan, Q and Ma, Y and Zhao, J and Hu, H},
title = {Mapping artificial intelligence in problem-based and case-based medical education: a bibliometric analysis (2019-2026).},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1901004},
pmid = {42598001},
issn = {2296-858X},
abstract = {INTRODUCTION: Problem-based learning (PBL) has been a cornerstone of medical education since its introduction at McMaster University in the 1960s. Since the public release of ChatGPT in November 2022, artificial intelligence (AI) tools have increasingly been applied to PBL and case-based learning (CBL) contexts, yet the research landscape at this intersection remains poorly characterized. This study aimed to map the growth trajectory, thematic structure, and collaboration networks of AI-PBL/CBL research from 2019 to 2026.

METHODS: A comprehensive search of Scopus and Web of Science was conducted on June 2, 2026, combining AI-related terms with PBL/CBL frameworks and medical education contexts. Using a PRISMA-guided bibliometric review workflow, 1,616 records were identified; after deduplication and eligibility screening, 735 unique publications (2019-2026, original articles, reviews, conference papers, and other eligible indexed document types) were included. Bibliometric analyses employed VOSviewer for network visualization (keyword co-occurrence, co-authorship, co-citation), CiteSpace for citation burst detection, and Bibliometrix for thematic mapping, three-field plot, and factorial analysis.

RESULTS: Publication output grew from 25 papers in 2022 to 254 in 2025, with 206 papers indexed by June 2, 2026. The United States (n = 70) and China (n = 64) led publication volume. Keyword co-occurrence analysis identified four thematic clusters: a central AI-focused cluster, a medical education and clinical reasoning cluster, a nursing and simulation-oriented cluster, and an educational technology cluster. Kung et al.'s 2023 study evaluating ChatGPT's performance on the USMLE was the most frequently co-cited reference (62 co-citations, betweenness centrality = 0.11). Thematic mapping positioned machine learning as a motor theme, while clinical reasoning, medical education, and self-directed learning appeared in the basic themes quadrant. The country/region collaboration network comprised 33 countries/regions and was led by the United States and China, although collaboration patterns remained uneven across regions.

CONCLUSION: To our knowledge, this is the first bibliometric study specifically focused on the intersection of AI technologies with PBL/CBL in health professions education. The findings reveal rapid growth after 2023, four distinct but interconnected research clusters, and a collaboration network led by the United States and China, with uneven regional participation. These results may inform curriculum design and research priorities in AI-enhanced medical education.},
}

@article {pmid42598675,
year = {2026},
author = {van de Zande, NA and Ruiter, CCC and Polman, MA and Brama, SCM and Roos, RAC and Kremer, PHC and de Bot, ST},
title = {Tracing neuroinflammation in neurodegeneration: insights from a scoping review on biofluid biomarkers.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag289},
pmid = {42598675},
issn = {2632-1297},
abstract = {Neuroinflammation is increasingly recognized as a key pathological process in neurodegenerative disease and can be monitored using biofluid biomarkers. Objective biomarkers may aid diagnosis, prognosis and progression. We conducted a scoping review of neuroinflammation biomarkers across major neurodegenerative diseases covering the past 23 years, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, Lewy body dementia, multiple system atrophy and progressive supranuclear palsy. PubMed and Web of Science were systematically searched for observational studies from 2003 to 2025 reporting neuroinflammation biomarkers in adult human subjects. Included markers encompassed blood, cerebrospinal fluid, saliva and urine, providing possible complementary information. Original studies on non-neuroinflammatory mechanisms, cellular or post-mortem biomarkers, animal models, genetics and comparisons between diseases were excluded. Two reviewers independently screened articles; biomarkers reported in ≥3 independent cohorts per disease were analysed. A total of 388 studies were included, predominantly in Alzheimer's disease/mild cognitive impairment (n = 214) and Parkinson's disease (n = 92). Eight biomarkers were most frequently reported: IL-6, TNF-α, IL-1β, CRP/hs-CRP, IL-10, MCP-1, YKL-40 and neutrophil-to-lymphocyte ratio (NLR), measured in blood or cerebrospinal fluid (CSF) as indicators of inflammatory processes associated with neurodegeneration. Across biomarkers, the strength and scope of evidence varied. Most studies demonstrated higher biomarker levels in disease, with more advanced stages, greater clinical severity and faster progression. NLR showed the most consistent pattern across staging, severity and progression, but is currently under-represented across diseases. CSF YKL-40 generally increased with disease presence and advancement; IL-6 showed consistent increases in advanced stages and with severity, although significant results were limited; MCP-1, CRP and TNF-α were mostly linked to severity and progression; IL-1β and IL-10 remained largely inconsistent. Other markers, including GFAP, showed associations in Alzheimer's disease but remain underexplored in other neurodegenerative diseases. Variability across studies, including differences in biofluid source, assay sensitivity, population characteristics and statistical approaches, limits interpretability and comparability. Although neuroinflammation is elevated in neurodegenerative diseases and generally intensifies as these diseases progress, potentially contributing to downstream pathology, the precise timing, role and predictive value of these biomarkers remain uncertain. A subset of markers, including NLR, YKL-40 and GFAP, shows relatively consistent associations and may warrant further investigation across diseases. In clinical practice, neuroinflammation biomarkers could serve as complementary tools to capture inflammatory processes related to disease heterogeneity and progression. Future longitudinal studies tracking pre-symptomatic and early-stage individuals, with standardized approaches, are needed to define temporal dynamics and explore their utility for monitoring disease progression and therapeutic response.},
}

@article {pmid42600995,
year = {2026},
author = {Ataei, R and Amini, J and Sanadgol, N and Simon, AF and Duennwald, ML},
title = {Circular RNAs in amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107574},
doi = {10.1016/j.nbd.2026.107574},
pmid = {42600995},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.},
}

@article {pmid42602697,
year = {2026},
author = {Sgobbi, P and de Rezende Pinto, WBV and Seneor, DD and Orsini, M and Chieia, MAT and Oliveira, ASB},
title = {Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1928302},
pmid = {42602697},
issn = {1664-2295},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Genetic Testing/methods/standards ; Brazil ; Genetic Predisposition to Disease ; *Practice Guidelines as Topic/standards ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a complex and progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons. Although most ALS cases occur sporadically, without a known family history of the disease, genetic factors play a major role in its pathogenesis through monogenic, oligogenic, or polygenic mechanisms. It is estimated that 10-15% of ALS cases occur in a familial setting; however, a specific monogenic cause cannot always be identified. Establishing the underlying genetic basis in both sporadic and familial ALS is essential, as it enables individualized and family genetic counseling, facilitates the early identification of at-risk or oligosymptomatic relatives, improves the prediction of gene-specific clinical trajectories, and, more recently, determines eligibility for gene-targeted therapies, such as tofersen for SOD1-associated ALS and ulefnersen, currently under clinical investigation, for FUS-associated ALS. Over the years, differing opinions have existed regarding the role of genetic testing in individuals diagnosed with ALS. However, accumulating clinical evidence has increasingly supported the timely and early implementation of genetic testing as part of the standard clinical management of patients with ALS. In this article, we present the perspective of leading Brazilian neurologists specializing in ALS care regarding the current role of genetic testing in clinical practice.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/diagnosis
*Genetic Testing/methods/standards
Brazil
Genetic Predisposition to Disease
*Practice Guidelines as Topic/standards

@article {pmid42604981,
year = {2026},
author = {Falcone, C and Arckens, L and Baiula, M and Bedini, A and Bocchi, R and Broadhead, MJ and Caprini, M and Cavaliere, F and Cesca, F and Chowdhury, HH and Ciuba, K and Civiero, L and Escartin, C and Ferroni, S and Formaggio, F and Frasca, A and Gratton, R and Holt, M and Iraci, N and Kreft, M and Leggio, L and Lia, A and Malik, AR and Min, R and Müller, FE and Murat, C and Pereira, MJ and Pekowska, A and Petrelli, F and Ramos-Gonzalez, P and Sanchez-Mico, MV and Smole, Z and Sokolova, D and Solas, M and Soldano, A and Szewczyk, LM and Torazza, C and Severino, FPU and Urrestizala-Arenaza, N and Zeug, A and Zhou, J and Zonta, M and Zorec, R and Verkhratsky, A and Gunhanlar, N},
title = {Written in the Stars: Astrocyte Biology From Evolution to Disease.},
journal = {Acta physiologica (Oxford, England)},
volume = {242},
number = {9},
pages = {e70289},
doi = {10.1111/apha.70289},
pmid = {42604981},
issn = {1748-1716},
support = {CNS2025-166813//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; RYC2021-033202-I//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; PID2023-146385NA-I00//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; PID2024-160537OB-I00//MICIU/AEI (Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación, Spain)/ ; 951923//European Commission (H2020)/ ; //European Union - NextGenerationEU/PRTR/ ; 2023.17564.ICDT//FCT (Fundação para a Ciência e a Tecnologia, Portugal)/ ; UMO-2018/01/H/NZ4/00001//National Science Centre (NCN, Poland)/ ; UMO-2021/43/B/NZ2/02934//National Science Centre (NCN, Poland)/ ; UMO-2021/42/E/NZ2/00392//National Science Centre (NCN, Poland)/ ; UMO-2023/51/D/NZ3/02998//National Science Centre (NCN, Poland)/ ; 2024/54/E/NZ4/00134//National Science Centre (NCN, Poland)/ ; 2024/53/B/NZ4/03058//National Science Centre (NCN, Poland)/ ; A2023021F//BrightFocus Foundation/ ; 2023.00418.BD//Fundação para a Ciência e a Tecnologia (FCT) doctoral fellowship/ ; G0C9922N//KU Leuven Research Council (C14/20/071) and the Research Foundation Flanders (FWO), Belgium/ ; },
mesh = {Humans ; *Astrocytes/physiology/pathology ; Animals ; *Biological Evolution ; *Brain ; *Neurodegenerative Diseases/metabolism/pathology ; *Nervous System Diseases ; },
abstract = {In the 21st century, neuroglial research has entered a period of Renaissance, extending the views of prominent neuroanatomists and neurologists of the 19th and early 20th centuries, who assigned to glial cells numerous physiological functions and highlighted their fundamental role in the pathophysiology of nervous system diseases. Astrocytes are highly diversified in structure and function; they control brain homeostasis, support synaptic connectivity, and enable information processing in neural networks. Evolutionary diversification of astrocytes, initially emerging as supportive cells of primitive sensory organs, drove a continuous expansion of astroglial complexity and functional versatility, ultimately making them indispensable neuroprotectors and homeostatic regulators. The large, morphologically elaborate astrocytes of the human brain arguably reflect an evolutionary response to increased neuronal homeostatic demands. Astrocytes are indispensable for synaptic function, serving as the principal regulators of neurotransmitter turnover and neuronal excitability. Astrocytes also govern brain energy metabolism, mitochondrial dynamics, and calcium signaling, thereby actively shaping cortical plasticity and circuits. Astrocytes are fundamental elements of the pathophysiology of neurological, neuropsychiatric, and neurodegenerative diseases, including Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, Rett syndrome, genetic astrocytopathies, and neurotrauma, where they demonstrate complex reactive changes directed at tissue preservation and regeneration, but which can also contribute to disease progression. Advances in single-cell transcriptomics, calcium imaging, chemogenetics, and iPSC-based models have transformed our understanding of astrocyte diversity and disease-specific dysfunction, opening new avenues of investigation. Given that no CNS disorder is known to occur without astrocyte involvement, multiple astrocyte-specific molecules represent compelling targets for cell-directed therapeutic strategies.},
}

Humans
*Astrocytes/physiology/pathology
Animals
*Biological Evolution
*Brain
*Neurodegenerative Diseases/metabolism/pathology
*Nervous System Diseases

@article {pmid42591225,
year = {2026},
author = {Vöhringer, K and Müller, MS and Yildiz, CB and Zimmer-Bensch, G},
title = {DNMT1 as an environmental sensor: epigenetic pathways linking environmental exposures, sex hormone signaling, and vulnerability to neurodevelopmental and neurodegenerative diseases.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1883887},
pmid = {42591225},
issn = {1664-2295},
abstract = {DNA methyltransferase 1 (DNMT1) has classically been viewed as the canonical maintenance methyltransferase, yet accumulating evidence positions it as a multifaceted hub that integrates environmental, hormonal, and metabolic signals with chromatin regulation in the developing and adult brain. This review highlights DNMT1 as an environmentally responsive epigenetic sensor across the lifespan. We examine how psychosocial stress, early-life adversity, inflammation, nutritional and microbiome-derived metabolites, and environmental toxicants modulate DNMT1 expression, subcellular localization, and post-translational modifications, thereby reshaping DNA methylation landscapes in neurons and glia. We further discuss how sex hormone signaling, particularly estrogen receptor alpha α (ERα)-DNMT1 feedback loops, introduces sex-specific dimensions to epigenetic responsiveness, and how lncRNAs serve as intermediaries linking environmental cues to targeted DNMT1 recruitment at specific genomic loci. Building on this framework, we review how DNMT1 dysregulation contributes to neurodevelopmental and neuropsychiatric disorders-including schizophrenia, autism spectrum disorder, and depression-and to neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and DNMT1-associated monogenic neurodegenerative disorders. By positioning DNMT1 as a molecular interface between genetic predisposition, environmental exposure, and circuit-level vulnerability, this review highlights the need for integrated, sex-stratified, and longitudinal approaches to understanding epigenetic risk in neurological disease.},
}

@article {pmid42595080,
year = {2026},
author = {Al-Badaineh, M and Josan, H and Imran, B and Ebeid, I and Mekhail, J and Abdou, M and Dagher, D and Ahmed, AF and Hantouly, A and Khan, M},
title = {Spin in Systematic Reviews on Patch-Augmented Rotator Cuff Repair: Prevalence, Predictors, and Methodological Implications.},
journal = {Journal of shoulder and elbow surgery},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jse.2026.07.030},
pmid = {42595080},
issn = {1532-6500},
abstract = {BACKGROUND: Rotator cuff tears are a major cause of shoulder pain and dysfunction, and surgical repair is often complicated by the risk of retear, especially in patients with large, massive, revision tears and high-risk patients. Biologic or synthetic patch augmentation has emerged to reinforce repair and potentially reduce retears. Despite many systematic reviews and meta-analyses on patch-augmented versus non-augmented repair, concerns remain regarding study heterogeneity, outcome variability, and spin in interpretation and reporting, particularly in abstracts. This study assessed the methodological quality and abstract spin.

METHODS: This systematic review was conducted in accordance with the Cochrane Handbook and PRISMA guidelines. On October 30, 2025, PubMed, Scopus, and Web of Science were searched for English-language systematic reviews and meta-analyses comparing patch- or graft-augmented versus non-augmented rotator cuff repair in clinical studies. Eligible reviews reported at least one clinical, patient-reported, or imaging-based outcome. Two reviewers independently performed duplicate study selection, data extraction, spin assessment, and methodological quality appraisal using Yavchitz et al.'s nine severe spin types and AMSTAR-2.

RESULTS: Sixteen reviews and meta-analyses were included in this study. Spin was identified in 81.3% (n = 13) of the abstracts. The types were 5 (62.5%), 3 (56.2%), and 8 (50.0%). Univariate analysis found no significant associations with the funding status (p = 0.36), quality (p = 1.00), or impact factor (p = 0.95). Each AMSTAR-2 flaw was associated with 61% more spin types (IRR 1.61; 95% CI 1.08-2.49; p = 0.02).

CONCLUSION: Spin is prevalent in the abstracts of systematic reviews on patch augmentation for rotator cuff repair, regardless of funding or journal impact factor. Although spin was widespread, poor methodological quality was linked to a greater spin burden rather than its presence. These findings highlight the importance of critically appraising systematic reviews, as spin may contribute to an overly favorable interpretation of the evidence and potentially influence clinical decision-making. Readers should interpret the conclusions cautiously and verify the claims against the full-text results.

LEVEL OF EVIDENCE: Research Methodology Study, Systematic Review.},
}

@article {pmid42588274,
year = {2026},
author = {Paynter, C and Mathers, S and Vogel, A and Cruice, M},
title = {Foregrounding Communication Access in Person-Centred Decision Making for People with Motor Neurone Disease: A Narrative Review.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {15},
pages = {},
pmid = {42588274},
issn = {2227-9032},
support = {1133541//NHMRC/MNDRA Postgraduate Scholarship/ ; FT220100253//Australian Research Council/ ; },
abstract = {Effective motor neurone disease (MND) management depends on patient and carer involvement in decisions about interventions and future care. Communication and cognitive impairments are common in MND and have under-recognised consequences for shared decision making and autonomy. This narrative conceptual review draws on empirical qualitative research with people living with MND and unpaid family carers and the literature specifically concerning shared decision making and communication in MND. Themes relating to communication, information use, and decision making styles were mapped onto an ALS/MND multidisciplinary decision making model. Enhancements to the model include expanding the decision making context beyond in clinical activity, embedding communication and cognitive skills and accommodations across stages, and acknowledging risks to collaborative decision making. Practical strategies for clinicians, healthcare services, people living with MND, and family carers are proposed to ensure that communication is foregrounded in-person-centred MND care. Observational and implementation research is required to evaluate and refine the proposed approaches.},
}

@article {pmid42533617,
year = {2026},
author = {Rasmussen, LK and Gomes Moreira, D and Okarmus, J and Simonsen, A and Meyer, M},
title = {Mitophagy in neurodegeneration: crosstalk between PRKN/parkin-dependent and PRKN-independent pathways.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-23},
doi = {10.1080/15548627.2026.2711596},
pmid = {42533617},
issn = {1554-8635},
abstract = {Mitochondrial quality control is essential for cellular homeostasis, particularly in neurons, where mitochondrial dysfunction is implicated in the pathogenesis of neurodegenerative diseases. Mitophagy, the selective degradation of damaged or superfluous mitochondria, plays a central role in maintaining mitochondrial integrity and metabolic balance. This review provides a comprehensive overview of the best-characterized PINK1-PRKN/parkin-dependent mitophagy pathway and the expanding repertoire of PRKN-independent mechanisms, including additional ubiquitin-dependent, receptor-mediated, and lipid-mediated pathways. We explore how these pathways intersect and compensate for one another, highlighting the complexity and adaptability of mitochondrial quality control networks. Furthermore, we discuss how dysregulated mitophagy contributes to the onset and progression of neurodegenerative diseases. By examining the interplay between mitophagy pathways and their regulation under physiological and pathological conditions, this review underscores the therapeutic potential of targeting mitophagy in neurodegeneration. Future studies should aim to decode the spatiotemporal dynamics of these pathways to uncover novel opportunities for clinical intervention.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMFR/GP78: autocrine motility factor receptor; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATG: autophagy related; Aβ: amyloid beta; BCL2L13: BCL2 like 13; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMc: core autophagy machinery components; CSNK2/CK2: casein kinase 2; DUB: deubiquitinase; DNM1L/DRP1: dynamin 1 like; FKBP8: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GABARAP: GABA type A receptor-associated protein; GLP-1: glucagon-like peptide 1; HD: Huntington disease; HUWE1: HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1; IMM: inner mitochondrial membrane; iPSC: induced pluripotent stem cell; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF5: membrane associated ring-CH-type finger 5; MCL1: MCL1 apoptosis regulator, BCL2 family member; MDV: mitochondria-derived vesicle; MFN1: mitofusin 1; MFN2: mitofusin 2; MQC: mitochondrial quality control; mtDNA: mitochondrial DNA; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; OMM: outer mitochondrial membrane; OMMAD: outer mitochondrial membrane-associated degradation; OPA1: OPA1 mitochondrial dynamin like GTPase; OPTN: optineurin; OXPHOS: oxidative phosphorylation; PARL: presenilin associated rhomboid like; PD: Parkinson disease; PE: phosphatidylethanolamine; PG: phagophore; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; PINK1: PTEN induced kinase 1; PPARGC1A/PGC-1α: PPARG coactivator 1 alpha; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RHOT1/Miro1: ras homolog family member T1; ROS: reactive oxygen species; SIAH1: siah E3 ubiquitin protein ligase 1; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TCA: tricarboxylic acid cycle; TFAM: transcription factor A, mitochondrial; TIMM: translocase of inner mitochondrial membrane; TOMM: translocase of outer mitochondrial membrane; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; UPRmt: mitochondrial unfolded protein response; UPS: ubiquitin-proteasome system; USP30: ubiquitin specific peptidase 30; VCP: valosin containing protein; VDAC: voltage dependent anion channel; WIPI: WD repeat domain, phosphoinositide interacting.},
}

@article {pmid42581131,
year = {2026},
author = {Rahim, A and Zubair, SM and Ahamed, M and Das, S and Patel, R and Debnath, B and Porel, P},
title = {cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders.},
journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology},
volume = {21},
number = {1},
pages = {},
pmid = {42581131},
issn = {1557-1904},
mesh = {Humans ; cGAS-STING Signaling Pathway ; Animals ; *Nucleotidyltransferases/metabolism/immunology ; *Membrane Proteins/metabolism/immunology ; *Nervous System Diseases/immunology/metabolism/drug therapy ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; STING Protein ; Signal Transduction ; },
abstract = {The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an essential cytosolic DNA-sensing system that plays an important role in the regulation of innate immune and inflammatory responses in the central nervous system (CNS). It was first discovered as a promising antiviral defense cascade and has since been shown to execute broader functions in neuroinflammation and neurodegeneration. The pathway can become hyperactive with the release of endogenous DNA from damaged nuclei, mitochondria, or genomic instability, leading to chronic production of type I interferon (TI-IFN), various pro-inflammatory cytokines, and eventually contributing to chronic neuroinflammatory diseases. Recent studies have found that dysregulated cGAS-STING signaling is associated with several neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), stroke, and age-related neurodegeneration. In the CNS, chronic activation of this pathway leads to activation of microglia, oxidative stress, breakdown of the blood-brain barrier (BBB), impaired function of the synapses, and neuronal death. Mitochondrial dysfunction and cytosolic release of mitochondrial DNA (mtDNA) further promote inflammatory signaling, thus perpetuating neurodegeneration. This review highlights the molecular and pathological mechanisms of cGAS-STING signaling in a broader aspect of neurological disorders and appraises the novel therapeutics already under development to inhibit this pathway to regulate neuroinflammation and enhance neurological outcomes.},
}

Humans
cGAS-STING Signaling Pathway
Animals
*Nucleotidyltransferases/metabolism/immunology
*Membrane Proteins/metabolism/immunology
*Nervous System Diseases/immunology/metabolism/drug therapy
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
STING Protein
Signal Transduction

@article {pmid42583074,
year = {2026},
author = {Glynne-Jones, R and Mawdsley, S},
title = {The historical perspective on anal cancer therapy: what have we learnt, where did we fail?.},
journal = {ESMO gastrointestinal oncology},
volume = {13},
number = {Pt A},
pages = {100151},
pmid = {42583074},
issn = {2949-8198},
abstract = {Squamous-cell cancer of the anus is a rare entity. Fifty years ago, understanding the natural history was limited by the lack of an agreed staging system and a largely irrelevant but complex histological categorisation. Retrospective reports described a small number of patients, generally with small tumours, treated by diverse methods with limited follow-up. The use of therapeutic radiation was limited by observed acute toxicity. Some centres gained substantial experience with interstitial radiation, but knowledge and expertise regarding the natural history and optimal methods of treatment were difficult to accumulate and hand on. Radiotherapy (RT) with or without interstitial radiation as the primary treatment, chemoradiotherapy (CRT) both definitive and preoperative, local excision for residual after CRT and small margin carcinomas and 'prophylactic' groin dissections after radical surgery all had advocates in different centres. The dogma in Europe at the time favoured split-course treatments. Early experiments combining fluoropyrimidines and RT were refined with Nigro et al.'s landmark study in 1974. Subsequent regimens are variations and today CRT with concurrent fluoropyrimidines and mitomycin C is accepted as the standard primary treatment. Early randomised phase III trials proved CRT to be more effective than external beam RT alone, but uncertainty remained over the optimal integration of chemotherapy, the type of chemotherapy, the ideal RT doses and potential late effects. These questions were imperfectly addressed and led to subsequent pragmatic phase III trials testing the impact of induction and consolidation chemotherapy and dose escalation. We describe the historical perspective and examine the opportunities we failed to grasp.},
}

@article {pmid42587774,
year = {2026},
author = {Garza, TN and Abisambra, JF},
title = {The Interactions of Tau, RNA, and Stress Granules in Neurodegenerative Disease: A Comprehensive Review.},
journal = {Cells},
volume = {15},
number = {15},
pages = {},
pmid = {42587774},
issn = {2073-4409},
support = {5T32AG061892-07/AG/NIA NIH HHS/United States ; 1R01AG075900-04/NH/NIH HHS/United States ; 1R01AG074584-05/NH/NIH HHS/United States ; 1R21AG093972-01/NH/NIH HHS/United States ; 5I50RX003000-07//United States Department of Veterans Affairs/ ; },
mesh = {Humans ; *tau Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/genetics/pathology ; *Stress Granules/metabolism ; *RNA/metabolism ; Animals ; RNA-Binding Proteins/metabolism ; },
abstract = {The discovery of RNA in the late 19th century revolutionized the understanding of cell biology. Subsequent discoveries over the next six decades revealed a key role for RNA in protein synthesis. Nevertheless, today, the mechanisms driving RNA metabolism remain enigmatic. Given its fundamental cellular role, RNA alterations are strongly linked to disease, including devastating neurodegenerative disorders pathologically defined by the accumulation of RNA-binding proteins. For example, the mislocalization of TDP-43, an RNA-binding protein, is a pathological feature of amyotrophic lateral sclerosis and frontotemporal dementia TDP-43. Another group of more than 20 neurodegenerative disorders, called tauopathies, is characterized by the aberrant accumulation of the protein tau. Similarly, the emerging concept that tau binds RNA, facilitating the formation of pathological structures, highlights the importance of RNA stability in tauopathies. However, the dynamics and consequences of RNA-tau interactions remain unclear. This review comprehensively catalogs key findings linking tau, RNA, and stress granules. These findings are important because they could offer novel opportunities to design therapeutic strategies.},
}

Humans
*tau Proteins/metabolism
*Neurodegenerative Diseases/metabolism/genetics/pathology
*Stress Granules/metabolism
*RNA/metabolism
Animals
RNA-Binding Proteins/metabolism

@article {pmid42576199,
year = {2026},
author = {Zheng, F and Guan, R and Yu, X and Yang, J and Zhao, H and Yang, F},
title = {ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.},
journal = {Cellular & molecular biology letters},
volume = {31},
number = {1},
pages = {},
pmid = {42576199},
issn = {1689-1392},
mesh = {Humans ; *RNA Editing/genetics ; *Adenosine Deaminase/metabolism/genetics ; *Central Nervous System Diseases/genetics/therapy/pathology/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; },
abstract = {The adenosine deaminases acting on RNA (ADAR) family of enzymes (ADAR1 and ADAR2) catalyze adenosine-to-inosine (A-to-I) RNA editing. This post-transcriptional change is remarkably prevalent in the central nervous system (CNS). ADAR-mediated editing is critical for proper brain development, synaptic plasticity, and immunological homeostasis in the central nervous system (CNS) via recoding neurotransmitter receptors and ion channels. Conversely, a wide range of CNS disorders, such as neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis), neuropsychiatric conditions (schizophrenia, bipolar disorder, and major depression), cerebrovascular diseases, and gliomas, are now linked to dysregulation of ADAR activity, whether through loss-of-function mutations, altered expression, or mislocalization. To address the main question of whether altered RNA editing is a fundamental driver of pathogenesis, a compensatory response, or a context-dependent modulator, this review critically synthesizes existing evidence. The basic processes of ADAR enzymes and their regulation throughout neurodevelopment are first described. Next, we thoroughly assess the unique molecular fingerprints of ADAR dysregulation across several CNS disorders, emphasizing recurring themes such as Alu RNA hypo-editing, induction of innate immunity, and GRIA2 editing, which can cause excitotoxicity. Lastly, we examine new treatment approaches that use or reinstate ADAR activity, such as small-molecule modulators and site-directed RNA editing tools (leveraging endogenous ADAR for programmable editing of RNA [LEAPER], clustered ADAR-recruiting guide RNAs (gRNAs) for effective RNA editing [CLUSTER], and mimicking inverted repeats to recruit ADARs using engineered oligoribonucleotides [MIRROR]). We summarize by reviewing key obstacles to clinical translation, including crossing the blood-brain barrier, the risks of off-target editing, and the challenges of achieving spatiotemporal accuracy. We also list important open topics for further investigation.},
}

Humans
*RNA Editing/genetics
*Adenosine Deaminase/metabolism/genetics
*Central Nervous System Diseases/genetics/therapy/pathology/metabolism
Animals
*RNA-Binding Proteins/metabolism/genetics

@article {pmid42576610,
year = {2026},
author = {Yang, Y and Yang, Y and Tang, Y and Yang, W},
title = {Myokines, Microbiota, and Neuroinflammation: Physical Activity Modulates the Gut-Brain Axis.},
journal = {Immunological investigations},
volume = {},
number = {},
pages = {1-28},
doi = {10.1080/08820139.2026.2689670},
pmid = {42576610},
issn = {1532-4311},
abstract = {BACKGROUND: Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are increasingly recognized as disorders influenced not only by intrinsic neural pathology but also by systemic physiological networks, including the gut-brain axis. Emerging evidence highlights physical activity as a potent modulator of this bidirectional communication system, with muscle-derived signals particularly myokines, metabolites, and extracellular vesicles playing a central role.

METHODS: This narrative review synthesizes current knowledge on how exercise-induced molecular mediators influence gut microbiota composition, intestinal barrier integrity, immune signaling, and neuroinflammatory pathways. Findings were integrated across the disciplines of neuroscience, microbiology, and exercise physiology to evaluate mechanistic links between muscle-secreted factors and gut-mediated responses.

RESULTS: Mechanistic links exist between muscle-secreted factors such as irisin, cathepsin B, BDNF-inducing pathways, and lactate with microbial metabolites including short-chain fatty acids. These interacting pathways demonstrate a combined impact on neuroprotection, synaptic plasticity, and the modulation of disease progression in neurodegenerative conditions.

CONCLUSION: Physical activity represents a promising non-pharmacological strategy for modulating the gut-brain axis in neurodegenerative conditions. Understanding the interplay between muscle-derived signals and gut-mediated pathways may open new avenues for targeted interventions aimed at slowing or preventing neurodegenerative decline.},
}

@article {pmid42580389,
year = {2026},
author = {Bu, J and Nie, X and Luo, H and Wang, J and Jiang, D and Xu, N and Zhuang, P and Zhang, Y and Yin, Q},
title = {Neuron-Derived Neuroinflammation in Neurodegenerative Diseases: Mechanisms and Intervention Prospects.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108383},
doi = {10.1016/j.phrs.2026.108383},
pmid = {42580389},
issn = {1096-1186},
abstract = {Neurodegenerative diseases represent a major global public health challenge, imposing substantial societal and economic burdens. Their complex pathogenesis and limited therapeutic options underscore an urgent need for new paradigms. Emerging evidence indicates that dysregulation of the brain's immune microenvironment is a critical driver of disease progression. Conventional wisdom posits that peripheral immune cells and central glial cells serve as the primary initiators of neuroimmune responses, whereas neurons are regarded merely as passive recipients of inflammatory damage. Emerging evidence suggests that upon receiving pathological signals in the central nervous system, neurons may become more vulnerable and participate in the onset of neuroimmune processes, positioning them as potential targets for early intervention in neurodegenerative diseases. This article systematically reviews the contribution of neuron-derived immune-inflammatory responses in neurodegenerative diseases and potential intervention strategies. We first outline the capacity of neurons to regulate neuroimmune responses and detail the underlying molecular mechanisms. Then we compare the specific mechanisms by which neurons with different susceptibility drive and amplify neuroinflammation in various neurodegenerative diseases such as alzheimer's disease, parkinson's disease, amyotrophic lateral sclerosis, vascular cognitive impairment, and transformed these mechanisms into intervention strategies targeting neurons,. This article aims to break through the traditional concept of passive neuronal damage, systematically integrate intervention strategies that shift from targeting peripheral immune and glial cells to regulating neuron-derived immunity, thereby providing a new theoretical framework for overcoming current clinical limitations and identifying effective therapeutic targets for the prevention and treatment of neurodegenerative diseases.},
}

@article {pmid42581113,
year = {2026},
author = {Jomova, K and Alomar, SY and Valko, R and Nepovimova, E and Kuca, K and Valko, M},
title = {Oxidative stress and inflammation in neurodegenerative disorders.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {42581113},
issn = {1432-0738},
abstract = {The brain's consumption of approximately 20% of the body's oxygen contributes to oxidative stress, a significant pathological factor in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This oxidative stress, linked to low levels of antioxidant enzymes, drives neuronal death by facilitating membrane peroxidation of fatty acids, proteins, and DNA. Alzheimer's disease is characterized by amyloid-beta (Aβ) plaque accumulation and hyperphosphorylated tau aggregates, both of which interact with mitochondria to generate reactive oxygen species (ROS). Aβ peptides bind metals such as iron and copper, catalyzing the formation of damaging hydroxyl radicals. Peripheral markers of oxidative damage, such as elevated malondialdehyde and protein carbonyls, are correlated with these processes in affected patients. In Parkinson's disease, the loss of dopaminergic neurons in the substantia nigra is associated with pathological iron accumulation and mitochondrial complex I dysfunction, which are worsened by misfolded α-synuclein and mutations in antioxidant genes such as PINK1 and Parkin. The autooxidation of dopamine also drives oxidative stress through the generation of hydrogen peroxide and reactive quinones. Huntington's disease involves the degeneration of medium spiny neurons in the striatum due to a polyglutamine repeat expansion in the huntingtin gene, which disrupts mitochondrial function and downregulates antioxidants, leading to excitotoxicity and ROS spikes. Amyotrophic lateral sclerosis primarily affects motor neurons due to the mutations in SOD1, which result in the production of aggregates that impair mitochondria and generate reactive nitrogen species (RNS), such as peroxynitrite. Mitigating oxidative stress in neurodegenerative disorders presents a considerable translational challenge. While low-molecular-weight antioxidant therapies for neurodegenerative disorders have shown promising results in preclinical and animal studies because they mitigate oxidative stress, their clinical efficacy is hampered by low bioavailability and difficulty in penetrating the blood‒brain barrier. To overcome these limitations, current medical research is focused on alternative delivery systems. Innovations such as nanoparticle-based drug delivery are being actively studied to help transport low-molecular-weight antioxidants across the blood‒brain barrier more safely and effectively. Several promising epidemiological trials linked high dietary intake of vitamins C and E to a reduced risk of Parkinson's disease, and plant-derived antioxidants such as polyphenols were explored for their ability to combat neuroinflammation and reduce cognitive decline. Refined oxidative stress-suppressing strategies involve the (ii) application of mitochondrial-targeted agents to preserve ATP production; (ii) boosting the Nrf2 pathway may trigger a cascade of detoxifying enzymes; (iii) supplementation with polyphenols such as quercetin, resveratrol, and curcumin can suppress oxidative stress and dampen microglial activation (neuroinflammation); (iv) and the use of substances affecting the bidirectional network linking oxidative stress and autophagy can clear ROS-generating components. Despite some promising epidemiological data, translating oral or systemic antioxidant therapy into effective clinical treatments for humans requires further effort. A survey of current knowledge of oxidative stress and antioxidant therapy in neurodegenerative diseases is the main subject of this review.},
}

@article {pmid42568821,
year = {2026},
author = {Okano, H},
title = {From neural development to regenerative medicine: A research journey in stem cell biology, spinal cord repair, and iPSC-based drug discovery.},
journal = {Regenerative therapy},
volume = {33},
number = {},
pages = {101157},
pmid = {42568821},
issn = {2352-3204},
abstract = {This commemorative article reflects on a research journey spanning neural development, stem cell biology, regenerative medicine, and iPSC-based drug discovery. My early work focused on RNA-mediated regulation in the nervous system, including studies on myelin basic protein gene regulation and the identification and functional characterization of the RNA-binding protein Musashi. These studies contributed to the conceptual foundation of neural stem cell biology and helped establish methods for identifying and isolating neural stem/progenitor cells, including those present in the adult human brain. Building on this foundation, my colleagues and I pursued translational research in spinal cord injury, ranging from analyses of injury pathophysiology and molecular interventions to preclinical studies using rodent and non-human primate models. These efforts ultimately led to the first-in-human clinical study of induced pluripotent stem cell-derived neural stem/progenitor cell transplantation for subacute spinal cord injury. In parallel, we developed patient-derived iPSC platforms for neurological disease modeling and drug discovery, particularly for amyotrophic lateral sclerosis, where iPSC-based screening identified Ropinirole as a therapeutic candidate and enabled reverse translational research linking cellular phenotypes with clinical responses. Looking ahead, I argue that the future of regenerative therapy will depend on the continued integration of developmental biology, stem cell science, disease modeling, rehabilitation, and clinical translation to address unmet medical needs in disorders of the central nervous system.},
}

@article {pmid42573824,
year = {2026},
author = {Su, B and Li, L and Zheng, X and Ma, H and Li, X and Feng, X},
title = {Clinical significance of SQSTM1 variants in ALS: report of p.Arg119Cys and literature review.},
journal = {Neurogenetics},
volume = {27},
number = {1},
pages = {},
pmid = {42573824},
issn = {1364-6753},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Sequestosome-1 Protein/genetics ; Male ; Middle Aged ; Pedigree ; Mutation, Missense ; Genetic Association Studies ; Adaptor Proteins, Signal Transducing/genetics ; },
abstract = {We analyzed the clinical features of a patient with amyotrophic lateral sclerosis (ALS) carrying a novel variant in the sequestosome 1 (SQSTM1) gene and explored the genotype-phenotype association of SQSTM1 gene variants in combination with previous literature. Clinical data and genetic testing results of an ALS patient treated at our hospital were collected. Whole-exome sequencing was used to screen for ALS-related genes, and candidate variants were validated by Sanger sequencing and family analysis. A systematic search was conducted in the PubMed database using the keywords ("amyotrophic lateral sclerosis") OR ("motor neuron disease") AND ("SQSTM1") to summarize the clinical and genetic characteristics of previously reported ALS patients with SQSTM1 variants. The patient was a 49-year-old male with progressive weakness in both lower limbs for one year and weakness in the left upper limb for the past three months. Electromyography showed extensive neurogenic damage. Genetic testing identified a novel heterozygous missense variant, c.355 C > T (p.Arg119Cys), in the SQSTM1 gene. Family verification revealed that his phenotypically normal mother carried the same variant. The literature search identified 58 cases of ALS associated with SQSTM1 variants. Missense variants were the most common type. We identified a novel SQSTM1 variant, c.355 C > T (p.Arg119Cys), in a ALS patient. Although this finding expands the variant spectrum, its pathogenicity remains uncertain and requires further functional validation and pedigree confirmation. Our literature review further shows that SQSTM1-associated ALS predominantly presents with limb onset, with a subset of patients exhibiting frontotemporal dementia or Paget's disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Sequestosome-1 Protein/genetics
Male
Middle Aged
Pedigree
Mutation, Missense
Genetic Association Studies
Adaptor Proteins, Signal Transducing/genetics

@article {pmid42576087,
year = {2026},
author = {Oyedokun, PA and Gbadero, JO and Ajao, DI and Olorunsesan, MD and Oyesiji, AI and Ayilara, GO and Ogunsina, MK and Justus, BS and Ademola, FM and Adetunji, EA and Okodio, PS and Amedu, NO},
title = {The Amino Acid-Neurodegeneration Axis: Excitotoxicity and Oxidative Stress as Context-Dependent Amplifiers of Metabolic Dysfunction.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42576087},
issn = {1559-1182},
mesh = {*Oxidative Stress/physiology ; Humans ; Animals ; *Amino Acids/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; *Nerve Degeneration/metabolism/pathology ; Mitochondria/metabolism ; },
abstract = {Homeostasis of amino acids is essential for the integrity of the CNS, and is maintained by a tightly regulated transport and metabolic circuit that ensures efficient neurotransmission, mitochondrial bioenergetics and redox homeostasis. Disruption of this equilibrium is associated with the pathogenesis of the major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Excessive glutamatergic stimulation and impaired glycine or homocysteine metabolism result in pathological Ca[2][+] influx, loss of mitochondrial membrane potential and production of reactive oxygen species, which are hallmarks of these disorders. It also limits cysteine availability and causes glutathione depletion, which affects antioxidant defence, and disrupts tryptophan-kynurenine metabolism, further affecting neurotoxic and neuroprotective signalling. Though there are disease-specific molecular triggers, the convergent pathogenesis of metabolic disruption makes neurons susceptible to disease. The convergent pathways link amino acid dysregulation to the reinforcement of each other's mechanisms of excitotoxicity, oxidative stress, mitochondrial dysfunction, and protein aggregation. Correcting the amino acid balance has clear translational potential for developing new therapies, such as glutathione augmentation, modulation of NMDA receptors, targeting of transporters, and regulation of metabolic enzymes. In addition, the use of metabolic biomarkers alongside neuroprotective endpoints in clinical trials could improve detection rates, patient stratification, and therapeutic precision. The concept of amino acid metabolism as a mechanism of neurodegeneration, therefore, provides a systems-level perspective and targets potential areas for continued neuroprotection and disease modification.},
}

*Oxidative Stress/physiology
Humans
Animals
*Amino Acids/metabolism
*Neurodegenerative Diseases/metabolism/pathology
*Nerve Degeneration/metabolism/pathology
Mitochondria/metabolism

@article {pmid42543164,
year = {2026},
author = {Wang, CY and Taylor, S and Pandya, VA and Clarke, BE and Pal, K and Shelkovnikova, TA and Wang, Y and Luisier, R and Patani, R},
title = {Intron retention in health and amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {149},
number = {8},
pages = {2604-2618},
pmid = {42543164},
issn = {1460-2156},
support = {Patani/Dec22/957-793/MNDA_/Motor Neurone Disease Association/United Kingdom ; MN5DF/2022/003//My Name'5 Doddie Foundation/ ; BB-2024-c4-l4//Target ALS/ ; //Francis Crick Institute/ ; FC010110//UK Medical Research Council/ ; Patani/Dec22/957-793//Motor Neuron Disease Association/ ; FC010110/CRUK_/Cancer Research UK/United Kingdom ; FC010110/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Introns/genetics ; Animals ; RNA Splicing/genetics ; },
abstract = {Intron retention (IR) is the molecular phenomenon by which introns, historically thought to represent non-coding 'junk', remain unspliced within pre-mRNA transcripts, resulting in their incorporation into the mature mRNA molecule. While the role of IR is well established in species of plant, fungi, insects and viruses, it remains relatively understudied in mammalian biology. It was previously assumed that IR only played a limited role in downregulating a transcript's translation potential through downstream initiation of nuclear detention or nonsense mediated decay (NMD). However, recent studies highlight IR's significantly more complex and dynamic contribution to cellular physiology and disease. In particular, a role for IR is emerging in both health and neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a rapidly progressive and invariably fatal disease that renders patients paralysed and unable to eat, speak or breathe. Significant technological advances now permit a comprehensive interrogation of previously unrecognized aspects of RNA metabolism in clinically relevant human cell types. In this review, we focus on the differential role(s) of nuclear and cytoplasmic intron retaining transcripts (nIRTs and cIRTs, respectively), as well as how IRTs may influence subcellular localization of ribonucleoprotein (RNP) complexes, loss of function of bound RNA binding proteins (RBPs) and liquid-liquid phase separation (LLPS) in physiology and disease. Additionally, we discuss the potential of IRTs as independent regulatory elements beyond their protein-coding functions and highlight how artificial intelligence is poised to accelerate discoveries in this area. In the context of IR's increasing appreciation, we also highlight its potential as a therapeutic target and explore current and future challenges in this burgeoning field.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism
*Introns/genetics
Animals
RNA Splicing/genetics

@article {pmid42558984,
year = {2026},
author = {Pourasghari, M and Babaie, S and Markazi-Movaghar, R and Salehpour, S and Eftekharsadat, B and Farshbaf-Khalili, A},
title = {The Effectiveness Based on Optimal Dose and Administration Route, and Safety Profiles of Stem Cells and Derived Products in the Treatment of Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Stem cells international},
volume = {2026},
number = {},
pages = {4122493},
pmid = {42558984},
issn = {1687-966X},
abstract = {BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effectiveness of stem cell therapies for patients with amyotrophic lateral sclerosis (ALS) based on optimal dosing and administration routes, as well as the safety profiles of stem cells and their derived products.

METHODS: The review followed PRISMA guidelines and involved a comprehensive literature search up to October 2025, receiving ethical approval from Tabriz University of Medical Sciences and registration in PROSPERO. It utilized international databases, including PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ProQuest, ClinicalTrials.gov, and Science Direct. The included studies comprised randomized controlled trials (RCTs), quasi-experimental studies, and other interventional designs involving ALS patients treated with stem cell therapies. In total, 31 studies were analyzed, featuring 7 controlled trials with 370 participants and 24 non-controlled pre-post studies with 460 participants. Heterogeneity was evaluated using I [2] statistics, and subgroup analyses were conducted based on treatment duration and dosing.

RESULTS: A pooled analysis (treatment group: n = 93; control group: n = 90) demonstrated a significant attenuation in the progression of disease severity, as measured by the ALS Functional Rating Scale (ALSFRS), in stem cell groups versus controls (weighted mean difference [WMD]: 8.89 95% CI: 4.12-13.67; p = 0.0003), which was beneficial for both the ≥10 × 10[6] and <10 × 10[6] dose sub-groups. However, a meta-analysis of single-arm studies in two control (pre-intervention) and intervention phases (n = 88) demonstrated no significant difference in progression of ALSFRS between study phases by time: month 3 (WMD: -1.27 (-3.01 to 0.47); p = 0.15), month 6 (WMD: -2.69 (-5.62 to 0.25); p = 0.07), month 9 (WMD: -1.55 (-3.49 to 0.39); p = 0.12), and month 12 (WMD: -7.59 (-13.95 to -1.26); p = 0.02). An accelerated decline in forced vital capacity (FVC) was observed during the intervention phase, with statistically significant reductions at month 3 (WMD: -10.91; 95% CI: -16.39 to -5.43; p < 0.0001) and month 6 (WMD: -15.97; 95% CI: -28.60 to -3.33; p = 0.01) compared with the pre-intervention control phase. Nevertheless, sensitivity analyses excluding studies involving high-dose mesenchymal stem cell (MSC) therapies demonstrated that these differences were no longer statistically significant. Moreover, no significant change in progression rate was observed at month 9 (WMD: -8.10 (-18.25 to 2.06); p = 0.12). The route of MSCs administration (intrathecal [IT], intramuscular [IM], and intravenous [IV]) had no effect on the results of ALSFRS and FVC, reinforced by sensitivity analyses. Adverse events were mostly mild, with headaches most frequent in high-dose groups.

CONCLUSION: Stem cell therapy for ALS appears to be safe, with preliminary evidence suggesting potential therapeutic benefit in slowing disease progression in selected patients. Nevertheless, the existing evidence base remains exploratory, and definitive conclusions regarding clinical effectiveness cannot yet be drawn. Future research should prioritize large-scale and multicenter RCTs with standardized cell manufacturing protocols and longer follow-up periods.},
}

@article {pmid42560011,
year = {2026},
author = {Abrar, F and Martin, DDO},
title = {Molecular switches of SQSTM1: the impact of post-translational modifications on autophagy and neurodegeneration.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/15548627.2026.2711593},
pmid = {42560011},
issn = {1554-8635},
abstract = {SQSTM1/p62 (sequestosome 1) is an important receptor protein involved in many cellular signaling processes, including macroautophagy/autophagy. It is a molecular hub for cellular homeostasis and cellular responses. Within autophagy, SQSTM1 targets ubiquitinated cargo for degradation, maintaining cellular proteostasis. Structurally, SQSTM1 consists of several domains that facilitate its binding to ubiquitinated cargo, the formation of SQSTM1 aggregate inclusions, interactions with MAP1LC3/LC3, and the mediation of clearance via the autophagy pathway. Beyond its structure, post-translational modifications of SQSTM1 dynamically regulate its function within a cell. Post-translational modifications - such as phosphorylation, ubiquitination, acetylation, S-acylation, and S-nitrosylation - are crucial for regulating SQSTM1 function, localization, and interaction with autophagic components, thereby influencing SQSTM1's role in the autophagy pathway. Understanding the role of these protein modifications in modulating autophagy may provide better insight into developing therapeutic strategies for diseases with dysregulated autophagy, such as neurodegenerative diseases. This review will discuss the role of these post-translational modifications in controlling SQSTM1's localization and function in autophagy.Abbreviations: ABHD = α/β-hydrolase domain; AD = Alzheimer Disease; ALS = amyotrophic lateral sclerosis; ATG = autophagy related ; CSNK2/CK2 = casein kinase 2; HD = Huntington Disease; HDAC/KDAC = histone deacetylase/lysine deacetylase; HTT = huntingtin; KAT = lysine acetyltransferase; KEAP1 = kelch like ECH associated protein 1; KIR = KEAP1-interacting region; LIR = LC3-interacting region; LYPLA/APT = lysophospholipase/acyl-protein thioesterase; MAP1LC3/LC3 = microtubule associated protein 1 light chain 3; MEF = mouse embryonic fibroblast; mHTT = mutant huntingtin; MTORC1 = MTOR complex 1; NBR1 = NBR1 autophagy cargo receptor; NEDD4 = NEDD4 E3 ubiquitin protein ligase ; NO = nitric oxide; NFE2L2/Nrf2 = nuclear factor erythroid 2-factor 2; PAT = palmitoyl acyltransferase; PB1 = Phox-BEM1 domain; PE = phosphatidylethanolamine; PLEKHM1 = pleckstrin homology and RUN domain containing M1; PLK2 = polo like kinase 2; PRKA/PKA = protein kinase cAMP-activated; PPT1 = palmitoyl-protein thioesterase 1; RB1CC1 = RB1 inducible coiled-coil 1; SNCA/α-synuclein = synuclein alpha; SNO = S-nitrosothiol; SOD1 = superoxide dismutase 1; SQSTM1 = sequestosome 1; TARDBP/TDP-43 = TAR DNA binding protein ; TBK1 = TANK binding kinase 1; TAX1BP1 = Tax1 binding protein 1; TRIM = tripartite motif containing ; UBA = ubiquitin-associated domain; UBE = ubiquitin-conjugating enzyme; ULK1 = unc-51 like autophagy activating kinase 1; UPS =ubiquitin-proteasome system; USP8 = ubiquitin specific peptidase 8; ZDHHC = zDHHC palmitoyltransferase.},
}

@article {pmid42567782,
year = {2026},
author = {Risby-Jones, G and Lee, JD and Fung, JN},
title = {Interleukin-6 trans-signalling as a selectively targetable driver of neurodegeneration.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.07.002},
pmid = {42567782},
issn = {1878-108X},
abstract = {Interleukin-6 (IL-6) exerts protective and pathogenic effects in the central nervous system through distinct receptor-signalling modes. Classical signalling via membrane-bound IL-6 receptor (IL-6R) is often associated with homeostatic and reparative functions, whereas trans-signalling, mediated by soluble IL-6R, expands IL-6 responsiveness to gp130-expressing cells and may promote chronic inflammation. Emerging evidence implicates dysregulated IL-6 trans-signalling in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Here, we review mechanisms linking IL-6 trans-signalling to immune, glial, neuronal, and vascular dysfunction in neurodegeneration. We highlight key knowledge gaps and discuss whether selective targeting of trans-signalling can limit inflammatory pathology while preserving beneficial classical IL-6 functions.},
}

@article {pmid42556956,
year = {2026},
author = {Rahman, U and Yang, SC},
title = {Management of Anastomotic Leaks: Endoscopic, Interventional, and Surgical Strategies.},
journal = {Advances in surgery},
volume = {60},
number = {1},
pages = {259-270},
doi = {10.1016/j.yasu.2026.03.017},
pmid = {42556956},
issn = {1878-0555},
mesh = {Humans ; *Anastomotic Leak/therapy/surgery/etiology ; },
abstract = {Anastomotic leaks (ALs) are a significant source of morbidity and mortality. Every step should be implemented to prevent AL, including careful patient selection, optimizing patient's clinical and nutritional status, and ensuring proper technique. The appropriate management of an AL depends on several factors, such as patient's clinical status, the type of surgery, location of the AL, induction therapies, and the resources available. Surgeons should be familiar with the armamentarium of treatment modalities available to manage AL and use a patient-tailored approach when selecting the most appropriate treatment.},
}

Humans
*Anastomotic Leak/therapy/surgery/etiology

@article {pmid42558527,
year = {2026},
author = {Li, S and Cao, T and Zhang, Q},
title = {Oxidative stress as a driver of organelle cascade damage in neurological diseases.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1892923},
pmid = {42558527},
issn = {1663-4365},
abstract = {As a core driver in the pathological progression of neurological diseases, oxidative stress contributes to the onset and development of multiple disorders, including traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), by inducing interconnected and bidirectional damage among mitochondria, endoplasmic reticulum, lysosomes, and the nucleus. This review systematically summarizes the oxidative stress-mediated inter-organelle crosstalk network: Mitochondria act as one of the earliest and central hubs, and their dysfunction (e.g., reactive oxygen species burst, calcium overload, and respiratory chain impairment) induces endoplasmic reticulum stress via ROS diffusion and calcium signaling disturbance. The disruption of endoplasmic reticulum calcium homeostasis further exacerbates mitochondrial damage, forming a vicious cycle. Lysosomes exhibit reduced membrane stability and impaired autophagic flux under oxidative stress, failing to clear damaged organelles and aggravating oxidative stress accumulation. Ultimately, oxidative stress signals are transmitted to the nucleus, resulting in DNA damage, aberrant epigenetic modifications, and activation of pro-inflammatory/pro-apoptotic genes, thereby accelerating disease progression. Notably, this organelle injury transmission is not a rigid unidirectional linear cascade; primary lysosomal or MAM defects can independently initiate the full organelle damage loop without preceding mitochondrial dysfunction. This review integrates current studies, clarifies context-dependent and disease-specific characteristics of organelle interactions, and discusses potential therapeutic strategies with critical consideration of translational challenges and limitations, providing a theoretical foundation for mechanistic research and clinical intervention of neurological diseases.},
}

@article {pmid42418847,
year = {2026},
author = {de La Seiglière, H and Letourneur, Æ and Ichas, F and De Giorgi, F},
title = {Phase separation and protein aggregation in neurodegenerative diseases.},
journal = {Biophysical chemistry},
volume = {338},
number = {},
pages = {107678},
doi = {10.1016/j.bpc.2026.107678},
pmid = {42418847},
issn = {1873-4200},
mesh = {Phase Separation ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates ; *Intrinsically Disordered Proteins/chemistry/metabolism/genetics ; alpha-Synuclein/metabolism/chemistry/genetics ; Animals ; tau Proteins/metabolism/chemistry/genetics ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, frontotemporal dementia, and ALS are characterized by amyloid protein aggregation involving intrinsically disordered proteins that are also capable of liquid-liquid phase separation (LLPS). LLPS, known to drive the formation of dynamic membraneless organelles essential for cellular functions, can play a role in limiting fibrillation process or aberrantly transition into solid aggregates under pathological conditions. Here we review how mutations, post-translational modifications, and environmental factors can modulate LLPS of proteins like Tau, TDP-43, FUS, and α-synuclein, potentially regulating amyloid aggregation. We also examine the interplay of these proteins exploring how LLPS and condensate maturation could impinge on the emergence of co-pathologies contributing to disease progression. Finally we discuss emerging therapeutic strategies, aimed at modulating phase separation dynamics.},
}

Phase Separation
Humans
*Neurodegenerative Diseases/metabolism/pathology
*Protein Aggregation, Pathological/metabolism
Protein Aggregates
*Intrinsically Disordered Proteins/chemistry/metabolism/genetics
alpha-Synuclein/metabolism/chemistry/genetics
Animals
tau Proteins/metabolism/chemistry/genetics

@article {pmid42549923,
year = {2026},
author = {Takahashi, M and Abe, T and Fujii, M},
title = {Targeting Ubiquitinated Protein Aggregates in Neurodegenerative Diseases: current Status and Future Directions.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/10985549.2026.2705871},
pmid = {42549923},
issn = {1098-5549},
abstract = {Various cellular stressors inhibit translation initiation and promote ribosome disassembly, thereby transiently inducing stress granules (SGs), dynamic ribonucleoprotein condensates that contain mRNAs and RNA-binding proteins. Although SG assembly is usually reversible, dysregulated SG dynamics can trigger the formation of persistent ubiquitin-positive protein inclusions. There is increasing evidence that this conversion of SGs into insoluble aggregates represents a central pathogenic mechanism in neurodegenerative proteinopathies, such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). TAR DNA-binding protein 43 (TDP-43) and Tau are causative factors in ALS and AD, respectively, and both localize to SGs under stress conditions. During disease progression, TDP-43 or Tau within SGs undergoes pathological changes that promote the formation of neurotoxic inclusions, which propagate neuronal dysfunction and death. This review summarizes recent advances in understanding the molecular factors that regulate SG assembly and disassembly, as well as the pathological processes that drive the conversion of SGs into aggregates associated with neurodegenerative diseases. Particular emphasis is placed on the role of the ubiquitin-specific protease 10 (USP10), which modulates SG dynamics and has been mechanistically implicated in both ALS and AD. Finally, we discuss the therapeutic potential of targeting these pathways to mitigate neurodegenerative disease progression.},
}

@article {pmid42552039,
year = {2026},
author = {Venu, G and A, VP and Justin, A},
title = {Molecular insights of peroxisome proliferator-activated receptor-γ signalling in amyotrophic lateral sclerosis and Huntington's disease.},
journal = {International review of neurobiology},
volume = {188},
number = {},
pages = {113-143},
doi = {10.1016/bs.irn.2026.05.014},
pmid = {42552039},
issn = {2162-5514},
mesh = {Humans ; *PPAR gamma/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Signal Transduction/physiology ; Animals ; *Huntington Disease/metabolism ; },
abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases like Huntingtons disease (HD) and Amyotrophic lateral sclerosis (ALS) which are caused by convergent mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy and dysregulated cell death pathways. Both conditions share significant disruptions in metabolic and inflammatory signalling despite having different genetic origins and clinical manifestations; underscoring the necessity of pathway-oriented treatment approaches. In the central nervous system, peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand-activated nuclear receptor has become an important regulator of inflammation, redox homeostasis, mitochondrial biogenesis and cellular stress responses. After giving a thorough overview of PPAR-γ structure activation and transcriptional regulation and the PGC-1α-mediated mitochondrial biogenesis axis, this chapter delves deeply into its interactions with major signalling pathways such as NF-κB, Wnt/β-catenin Nrf2/ARE and the autophagy-apoptosis networks. With a focus on experimental data showing PPAR-γ signaling's neuroprotective, anti-inflammatory, antioxidant and metabolic regulatory roles the pathophysiology of ALS and HD is critically investigated. Lastly the need for improved biomarkers, tailored multi-target strategies and selective modulators is highlighted in the discussion of current therapeutic limitations and translational difficulties.},
}

Humans
*PPAR gamma/metabolism
*Amyotrophic Lateral Sclerosis/metabolism
*Signal Transduction/physiology
Animals
*Huntington Disease/metabolism

@article {pmid42552041,
year = {2026},
author = {Khodve, G and Raval, S and Banerjee, S},
title = {Intestinal microbiota in neurodegeneration and ageing: Mechanisms, pathways, and therapeutic interventions.},
journal = {International review of neurobiology},
volume = {188},
number = {},
pages = {199-229},
doi = {10.1016/bs.irn.2026.05.015},
pmid = {42552041},
issn = {2162-5514},
mesh = {Humans ; *Neurodegenerative Diseases/microbiology/metabolism/immunology/diet therapy/therapy ; *Aging/metabolism/immunology ; *Gastrointestinal Microbiome/physiology ; Animals ; *Dysbiosis/metabolism/immunology ; *Brain-Gut Axis/physiology ; Probiotics ; Brain/metabolism ; },
abstract = {The human gut microbiota represents a complex ecosystem of trillions of microorganisms with profound implications for neurological health. Emerging evidence demonstrates that dysbiosis, an imbalance in microbial composition and function, plays a crucial role in the pathogenesis of neurodegenerative diseases and age-related cognitive decline. This chapter summarizes current knowledge of the microbiota-gut-brain axis (MGBA) and elucidates how intestinal microbes and their metabolites communicate with the central nervous system via neural, immune, endocrine, and metabolic pathways. We examine the mechanistic links between gut dysbiosis and specific neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Multiple sclerosis (MS). Furthermore, we explore age-related changes in the microbiota and their contributions to neuroinflammation, immunosenescence, and cognitive decline. Finally, we evaluate therapeutic interventions targeting the microbiota, including probiotics, prebiotics, synbiotics, and dietary modulation as promising strategies to prevent and ameliorate neurodegenerative pathology. The chapter provides a comprehensive summary of how microbiota-targeted approaches may delay ageing and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/microbiology/metabolism/immunology/diet therapy/therapy
*Aging/metabolism/immunology
*Gastrointestinal Microbiome/physiology
Animals
*Dysbiosis/metabolism/immunology
*Brain-Gut Axis/physiology
Probiotics
Brain/metabolism

@article {pmid42553297,
year = {2026},
author = {Li, Q and You, M},
title = {Targeting mitochondria for the treatment of neurodegenerative diseases.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1835506},
pmid = {42553297},
issn = {1662-4548},
abstract = {Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.},
}

@article {pmid42548241,
year = {2026},
author = {Konarbayeva, Z},
title = {Rheological and Technological Design of Texture-Modified Food Systems for Dysphagia Management in Amyotrophic Lateral Sclerosis.},
journal = {Journal of texture studies},
volume = {57},
number = {4},
pages = {e70105},
pmid = {42548241},
issn = {1745-4603},
mesh = {*Deglutition Disorders/etiology/diet therapy ; *Amyotrophic Lateral Sclerosis/complications ; *Rheology ; Humans ; Viscosity ; *Food Technology ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is frequently accompanied by progressive dysphagia, weight loss, and hypermetabolism, which complicate the maintenance of adequate nutritional status. For these patients, food systems must not only provide sufficient energy and protein within a limited volume but also exhibit textural and rheological properties that support safe swallowing. This review analyzes technological and rheological approaches to the design of texture-modified food systems for nutritional support in ALS. Particular attention is given to apparent viscosity, shear-thinning behavior, yield stress, structural homogeneity, and storage stability as parameters affecting bolus formation, swallowing safety, and product performance. The relevance of the International Dysphagia Diet Standardization Initiative framework for classifying food textures and liquid consistencies is also considered. The review further examines the functional and technological roles of animal- and plant-based raw materials, including regional raw materials, in the formulation of energy-dense and structurally stable foods. Proteins, lipids, hydrocolloids, starch gels, and polysaccharide networks are discussed as key components for controlling texture, viscosity, gelation, emulsion stability, and nutritional density. Technological strategies such as homogenization, emulsification, protein-based structuring, hydrocolloid thickening, high-pressure homogenization, and 3D food printing are considered in relation to their potential for developing safe, acceptable, and locally adaptable products for patients with ALS-related dysphagia. The findings highlight the need to integrate food texture science, rheological control, nutritional adequacy, sensory acceptability, and regional availability in the development of clinically relevant texture-modified foods.},
}

*Deglutition Disorders/etiology/diet therapy
*Amyotrophic Lateral Sclerosis/complications
*Rheology
Humans
Viscosity
*Food Technology
Animals