@article {pmid41904009,
year = {2026},
author = {Chinnathambi, S and Malik, S},
title = {Cytoskeltal intermediate filaments in Tau pathology and neurodegeneration.},
journal = {Advances in protein chemistry and structural biology},
volume = {150},
number = {},
pages = {351-376},
doi = {10.1016/bs.apcsb.2025.10.028},
pmid = {41904009},
issn = {1876-1631},
mesh = {Humans ; *Intermediate Filaments/metabolism/pathology ; *tau Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Cytoskeleton/metabolism/pathology ; Alzheimer Disease/metabolism/pathology ; Intermediate Filament Proteins/metabolism ; },
abstract = {Intermediate filaments are cytoskeletal proteins that are vital for proper cell structure formation and functioning. There are six types of these proteins. Type I includes acidic keratins, Type II includes basic and neutral keratins, both of which are present in epithelial cells. Type III includes vimentin, desmin, glial fibrillary acidic protein and peripherin, among which the last two are highly involved in neurodegenerative diseases. Type IV includes three types of neurofilament proteins, NF-L, NF-M and NF-H, where L signifies light, M signifies medium and H signifies heavy. The fourth protein in this category is α-internexin. All of these proteins are highly involved in neurodegenerative diseases, especially the neurofilament proteins. The type V intermediate filament proteins are lamins. The type VI intermediate filaments are nestins. Their involvement in a variety of neurodegenerative diseases has been observed, including Alzheimer's disease, Cerebral Ischemia, Multiple Sclerosis, Alexander Disease, Neuronal IF inclusion disease (NIFID) and Amyotrophic Lateral Sclerosis (ALS). Alzheimer's disease is a neurodegenerative disease in which two proteins are mainly involved, the Tau protein and the Amyloid-β protein. This review discusses the crosstalk of the intermediate filament proteins with the pathological proteins involved in the neurodegenerative diseases. For the case of the Alzheimer's disease, many of the intermediate filament proteins are involved in the disease pathology and are vital markers for the disease. One of the category of proteins involved is neurofilaments, among which NF-L is a marker for the disease. Keratin 9 and the glial fibrillary acidic protein (GFAP) are other intermediate filament proteins that are being explored as markers for the Alzheimer's disease.},
}

Humans
*Intermediate Filaments/metabolism/pathology
*tau Proteins/metabolism
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Cytoskeleton/metabolism/pathology
Alzheimer Disease/metabolism/pathology
Intermediate Filament Proteins/metabolism

@article {pmid41904011,
year = {2026},
author = {Selvaraj, C and Desai, D and Sumitha, E},
title = {The quest to restore neuronal structure: Targeting cytoskeletal proteins in neurodegenerative diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {150},
number = {},
pages = {397-422},
doi = {10.1016/bs.apcsb.2025.10.026},
pmid = {41904011},
issn = {1876-1631},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; *Cytoskeletal Proteins/metabolism/genetics/antagonists & inhibitors ; Animals ; *Neurons/metabolism/pathology ; Cytoskeleton/metabolism ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease are characterized by progressive neuronal dysfunction and loss. A growing body of evidence implicates cytoskeletal disruption as a central pathological mechanism in these conditions. Cytoskeletal proteins, including microtubules, actin filaments, tau, neurofilaments, and alpha-synuclein, not only provide structural integrity but also regulate axonal transport, synaptic connectivity, and neuroplasticity. Its dysfunction will lead to impaired intracellular trafficking, protein aggregation, and neuronal degeneration. This chapter explores clearly about the specific cytoskeletal abnormalities that are evident in major neurodegenerative disorders, highlighting the biological mechanisms such as tauopathy-induced microtubule instability in Alzheimer's, actin cytoskeleton dysregulation in Parkinson's, and neurofilament aggregation in ALS. Current therapeutic strategies aimed at the stabilizing cytoskeletal components, enhancing protein clearance, and restoring transport dynamics are examined, alongside the cutting-edge approaches including the gene therapy, CRISPR/Cas9 editing, and nanotechnology-based delivery systems. Challenges such as limited blood-brain barrier penetration, off-target toxicity, and patient heterogeneity are also discussed with the focus on need for precision medicine. Additionally, we have also explored the future directions that specifically focused on the biomarker development, combination therapies, and strategies to promote neuroregeneration and structural plasticity. Targeting cytoskeletal pathways holds significant promise not only for suppressing the disease progression but also for rebuilding the structural foundation of the nervous system, potentially reversing the neurodegenerative decline.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology/therapy
*Cytoskeletal Proteins/metabolism/genetics/antagonists & inhibitors
Animals
*Neurons/metabolism/pathology
Cytoskeleton/metabolism

@article {pmid41906147,
year = {2026},
author = {Zhou, X and Yu, P and Shen, X},
title = {m6A RNA methylation in neural plasticity, brain aging, and neurodegenerative vulnerability.},
journal = {Molecular brain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13041-026-01297-z},
pmid = {41906147},
issn = {1756-6606},
support = {82471208 and 82171184//National Natural Science Foundation of China/ ; },
abstract = {m6A is a pervasive post-transcriptional RNA modification that regulates RNA splicing, stability, localization, and translation in the brain. In this review, we outline the core m6A regulatory machinery and summarize its spatial organization across neurons and glial cells, highlighting established roles in brain development, synapse formation, and axon growth. We then focus on experience-dependent plasticity, synthesizing evidence that neuronal activity and environmental inputs dynamically reshape m6A to regulate immediate-early transcription and local translation at synapses across sensory, cognitive, emotional, and motor domains. With aging, m6A programs are reconfigured in a cell-type-specific manner, a shift associated with reduced plasticity and increased vulnerability. We further survey disease-associated alterations in m6A across Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke-related cognitive impairment, ALS and FTD, as well as metal or toxin exposure, emphasizing convergent effects on dopaminergic and glutamatergic signaling, synaptic integrity, inflammation, and cellular stress responses. Finally, we discuss emerging opportunities and conceptual challenges in targeting m6A enzymes or reader proteins, and outline priorities for future work, including cell-type- and subcellular-resolved mapping, causal perturbation in defined circuits and life stages, and the development of biomarkers and selective modulators. Together, these observations position m6A as a molecular interface linking experience-dependent plasticity, brain aging, and neurodegenerative vulnerability.},
}

@article {pmid41900026,
year = {2026},
author = {Jamerlan, A and Hulme, J},
title = {Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {6},
pages = {},
pmid = {41900026},
issn = {1420-3049},
support = {RS-2025-02292973//Korea Institute of Marine Science and Technology Promotion/ ; RS-2021-NR060117//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Autophagy/drug effects ; *TDP-43 Proteinopathies/metabolism/drug therapy/pathology ; Lysosomes/metabolism ; Animals ; *DNA-Binding Proteins/metabolism/genetics ; Oligonucleotides, Antisense/pharmacology ; Proteolysis ; },
abstract = {The cytoplasmic accumulation of TDP-43 aggregates remains a persistent pathological hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). The cell's natural clearance mechanisms, the Ubiquitin-Proteasome System (UPS) and the autophagy-lysosome pathway (ALP), are hypothesized to fail, at least in part, due to the sequestration of key components of these pathways by pathological TDP-43 species, thereby impairing autophagosome-lysosome fusion and lysosomal competence. Classical autophagic activators (e.g., rapamycin) can initiate upstream steps in the pathway but cannot address downstream flux bottlenecks, limiting their ability to restore effective TDP-43 clearance. This review revisits classical strategies and discusses newer approaches to modulate TDP-43 clearance, including transcription factor EB (TFEB) activators, proteolysis-targeting chimeras (PROTACs), and antisense oligonucleotides (ASOs). We propose that adopting multi-targeting strategies and developing better biomarkers are vital for clinical success.},
}

Humans
*Autophagy/drug effects
*TDP-43 Proteinopathies/metabolism/drug therapy/pathology
Lysosomes/metabolism
Animals
*DNA-Binding Proteins/metabolism/genetics
Oligonucleotides, Antisense/pharmacology
Proteolysis

@article {pmid41901170,
year = {2026},
author = {Kwaśniewska, K and Fic, W and Polak-Szczybyło, E},
title = {Vitamins as Modulators of Neurodegenerative Disease Pathways: Mechanisms and Therapeutic Perspectives.},
journal = {Nutrients},
volume = {18},
number = {6},
pages = {},
pmid = {41901170},
issn = {2072-6643},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Vitamins/therapeutic use/pharmacology/administration & dosage ; *Neuroprotective Agents/pharmacology ; *Dietary Supplements ; Antioxidants ; Oxidative Stress/drug effects ; Ubiquinone/analogs & derivatives ; Animals ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, currently represent one of the major challenges in contemporary medicine and geriatrics. Progressive degeneration of the nervous system affects not only patients' physical functioning but also their psychosocial well-being, often leading to social isolation and disruption of interpersonal relationships. These processes are most strongly associated with individuals over 65 years of age, in whom metabolic syndrome is frequently diagnosed and constitutes a significant factor predisposing them to the exacerbation of neuropathological changes. This review analyzes the role of selected vitamins in modulating the course of neurodegenerative disorders, with particular emphasis on their neuroprotective potential. Specific attention is given to their involvement in antioxidant defense mechanisms, regulation of inflammatory pathways, prevention of abnormal protein aggregation, participation in neurotransmitter synthesis, and support of mitochondrial function and cellular energy metabolism. The review also considers key interactions between vitamins and coenzyme Q10, which synergistically enhance neuroprotective mechanisms. Deficiencies in certain vitamins may exacerbate oxidative stress, impair synaptic transmission, and intensify neuroinflammatory responses, thereby contributing to disease progression. The study analyzes the available data on therapeutic doses of vitamins and compares them with the recommended dietary intake and the upper tolerable intake levels (UL). The available evidence suggests that personalized vitamin supplementation, when integrated with a well-balanced and nutrient-dense diet, may constitute a valuable adjunctive therapeutic strategy. Such an approach may help attenuate disease progression, support neuronal integrity, and improve functional outcomes. Ultimately, targeted nutritional interventions may enhance overall well-being and quality of life in patients affected by neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
*Vitamins/therapeutic use/pharmacology/administration & dosage
*Neuroprotective Agents/pharmacology
*Dietary Supplements
Antioxidants
Oxidative Stress/drug effects
Ubiquinone/analogs & derivatives
Animals

@article {pmid41904003,
year = {2026},
author = {Kinger, S and Choudhary, A and Kumar, P and Jagtap, YA and Sharma, V and Dhiman, R and Prasad, A and Verma, R and Chinnathambi, S and Mishra, A},
title = {Molecular chaperones mediated proteostasis depletion: A cause of neurodegeneration?.},
journal = {Advances in protein chemistry and structural biology},
volume = {150},
number = {},
pages = {181-219},
doi = {10.1016/bs.apcsb.2025.10.033},
pmid = {41904003},
issn = {1876-1631},
mesh = {Humans ; *Proteostasis ; *Neurodegenerative Diseases/metabolism/pathology ; *Molecular Chaperones/metabolism ; Animals ; },
abstract = {Protein homeostasis is a critical aspect of cellular homeostasis as proteins are one of the most diverse biomolecules, responsible for multiple molecular and cellular functions. Protein quality control machinery is essential for maintaining integrity of cellular proteome via regulating its synthesis, structure, function, and degradation. Molecular chaperones are central to the protein quality control apparatus of cells and assist in folding nascent polypeptides, maturation, sequestration, solubilisation, and degradation of proteins. The coordination and cooperation between multiple cellular chaperones and other quality control elements, such as ubiquitin-proteasome system and autophagy, form a network, critical for proteostasis. Disturbed proteostasis and protein aggregation are hallmark features of neurodegenerative diseases. Re-establishing cellular proteostasis and enhancing chaperones' levels and functions can alleviate protein aggregation and associated cytotoxicity. Here, we have explored the potential of abundant cellular chaperone Hsp90, large chaperone Hsp110, small chaperone Hsp27, and anti-oxidant and mitoprotective chaperone DJ-1 in the regulation of proteostasis, with implications for neurodegenerative diseases, Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. We have focused on roles and mechanisms of function of these chaperones in countering disturbed proteostasis in neurodegenerative disorders.},
}

Humans
*Proteostasis
*Neurodegenerative Diseases/metabolism/pathology
*Molecular Chaperones/metabolism
Animals

@article {pmid41898412,
year = {2026},
author = {Rakovskaya, A and Volkova, E and Pchitskaya, E},
title = {Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
pmid = {41898412},
issn = {1422-0067},
support = {25-74-10019//Russian Science Foundation/ ; },
mesh = {Humans ; *Calcium Signaling ; *Cytoskeleton/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Neurons/metabolism/pathology ; Calcium/metabolism ; },
abstract = {Neuronal function relies on the precise coordination between intracellular calcium (Ca[2+]) signaling and the cytoskeletal architecture that underpins synaptic transmission, plasticity, and structural stability. Disruption of this calcium-cytoskeleton interplay has been noted in numerous neurodegenerative diseases. We discuss how Ca[2+]-dependent cytoskeletal remodeling governs long-term potentiation and depression, dendritic spine morphology, and presynaptic function, highlighting the functions of end-binding proteins, STIM (Stromal Interaction Molecule)/Orai-mediated store-operated calcium entry, and the spine apparatus. Disease-specific manifestations of cytoskeletal-calcium dysregulation are reviewed across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, tauopathies, and prion disorders. Finally, we evaluate emerging therapeutic strategies targeting calcium homeostasis, cytoskeletal dynamics, and their downstream effectors, including multi-target approaches.},
}

Humans
*Calcium Signaling
*Cytoskeleton/metabolism
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Neurons/metabolism/pathology
Calcium/metabolism

@article {pmid41898662,
year = {2026},
author = {Katz, M and Robertson, T and Ngo, ST and Yarlagadda, S and Henderson, RD and McCombe, PA and Noakes, PG},
title = {Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
pmid = {41898662},
issn = {1422-0067},
support = {DIS-202403-01216//Fight MND/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism ; Humans ; Animals ; *Muscle, Skeletal/pathology/metabolism ; Neuromuscular Junction/pathology/metabolism ; Motor Neurons/pathology/metabolism ; Disease Models, Animal ; Biomarkers/metabolism ; },
abstract = {In amyotrophic lateral sclerosis (ALS), a central event is the withdrawal of the motor nerve terminal from its target muscle. Whether this defect is driven by faults in the motor neuron or faults that originate within the muscle remains an area of investigation. In this review, we focus on the pathological abnormalities that are found in skeletal muscle, focusing, when possible, on human ALS, with support from ALS animal models. We begin with an overview of skeletal muscle, including a review of muscle fiber type, motor units and the neuromuscular synapse. Next, we provide a description of the clinical and biomarker changes that occur in the muscles of patients with ALS. We provide an extensive account of the histopathological changes that are evident in ALS muscle, such as fiber type grouping, muscle inflammation, protein misfolding, mitochondrial dysfunction, and alterations in neuromuscular junctions and muscle satellite cells. Our review then concludes with an update of metabolic and molecular-genetic changes that are found in ALS muscle. The evidence shows that muscle can be an additional target for therapy in ALS, in combination with therapies targeting neurons and glia within the central nervous system (CNS).},
}

*Amyotrophic Lateral Sclerosis/pathology/metabolism
Humans
Animals
*Muscle, Skeletal/pathology/metabolism
Neuromuscular Junction/pathology/metabolism
Motor Neurons/pathology/metabolism
Disease Models, Animal
Biomarkers/metabolism

@article {pmid41895273,
year = {2026},
author = {Kim, D and Kondo, T and Inoue, H},
title = {Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102866},
doi = {10.1016/j.stemcr.2026.102866},
pmid = {41895273},
issn = {2213-6711},
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss. Microglia, the brain's resident macrophages, are key contributors to disease pathogenesis, with many genetic risk variants enriched in microglia-specific genes. While rodent models have provided valuable insights, human induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) technologies now enable the generation of human microglia-like cells, offering a physiologically relevant platform to study human microglial biology. This review discusses the developmental origins and functions of microglia, current differentiation approaches, and how these models help elucidate disease-relevant phenotypes and molecular mechanisms in neurodegeneration.},
}

@article {pmid41898328,
year = {2026},
author = {Nesci, S},
title = {Mitochondrial Dysfunction in the Inflammatory Process of Neurodegenerative Diseases.},
journal = {Biomedicines},
volume = {14},
number = {3},
pages = {},
pmid = {41898328},
issn = {2227-9059},
abstract = {Neurodegenerative diseases share a mitochondrial-immune axis in which impaired oxidative phosphorylation reshapes neuronal metabolism and drives chronic inflammation. Complex I play a redox gatekeeper role at the coenzyme Q (CoQ) junction: catalytic defects, misassembly, or reverse electron transport over-reduce the CoQ pool, increase electron leak, and elevate ROS. How respiratory supercomplex plasticity (CI-CIII2, CIII2-CIVn, or CI-CIII2-CIVn) modulates carrier channelling, flux control, and ROS propensity through dynamic reorganization of the electron transport chain is highlighted. Excess ROS damages lipids and mitochondrial DNA, promoting the release of mitochondrial damage-associated molecular patterns s that activate NLRP3 inflammasome signalling, cGAS-STING-dependent interferon programs, and endosomal TLR9 pathways, establishing feed-forward loops between mitochondrial injury and neuroinflammation. Disease-focused sections integrate evidence from Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and Huntington's models, and map these mechanisms onto therapeutic opportunities spanning electron transport chain support, supercomplex stabilization, and consider mtDNA-sensing inflammatory nodes.},
}

@article {pmid41885638,
year = {2026},
author = {Sadhukhan, A and Chauhan, A and Kumar, M and Singh, TG and Mujwar, S and Awasthi, A},
title = {Cryptoxanthin as a multitarget neuroprotective agent: mechanistic and in silico perspectives.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {3},
pages = {},
doi = {10.1093/jpp/rgag029},
pmid = {41885638},
issn = {2042-7158},
mesh = {*Neuroprotective Agents/pharmacology/therapeutic use ; Humans ; Molecular Docking Simulation ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Xanthophylls/pharmacology/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Computer Simulation ; },
abstract = {OBJECTIVES: Neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS) are complex disorders driven by multiple pathological processes, including oxidative stress, mitochondrial dysfunction, protein misfolding, and neuroinflammation. Due to this multifactorial nature, there is a growing interest in identifying natural compounds with multi-targeted neuroprotective properties. This review aims to evaluate the therapeutic potential of β-cryptoxanthin, a naturally occurring xanthophyll carotenoid, as a candidate molecule for mitigating neurodegenerative diseases.

METHODS: A comprehensive literature review was conducted to examine the neuroprotective mechanisms of β-cryptoxanthin, focusing on its antioxidant, anti-inflammatory, and immunomodulatory properties. In addition, in silico molecular docking studies were performed using AutoDock Vina to investigate the binding interactions of β-cryptoxanthin with key molecular targets associated with inflammation and neurodegenerative pathways.

KEY FINDINGS: β-Cryptoxanthin demonstrated strong neuroprotective potential due to its ability to scavenge reactive oxygen species (ROS) and modulate key molecular pathways involved in neuroinflammation and oxidative damage. Structurally characterized by a hydroxylated β-carotene backbone with 11 conjugated double bonds, β-cryptoxanthin showed favorable binding affinities with several inflammation- and neurodegeneration-related targets, including COX-2 (-11.6 kcal/mol), PI3K (-9.6 kcal/mol), mTOR1 (-9.2 kcal/mol), and GSK-3β (-8.7 kcal/mol). Additionally, interactions with JAK2, MAPK1, NF-κB, NRF2, and TLR4 suggest its involvement in regulating neuroimmune signalling pathways and inflammatory mediators.

CONCLUSIONS: The findings of this review highlight β-cryptoxanthin as a promising candidate for future neurotherapeutic investigation due to its multi-targeted mechanisms of action against key pathways implicated in neurodegeneration. Molecular docking results support its potential mechanistic role in modulating inflammation- and oxidative stress-related targets. However, these findings represent mechanistic plausibility rather than confirmed clinical efficacy, and further validation through preclinical and clinical studies is required.},
}

*Neuroprotective Agents/pharmacology/therapeutic use
Humans
Molecular Docking Simulation
*Neurodegenerative Diseases/drug therapy/metabolism
*Xanthophylls/pharmacology/therapeutic use
Animals
Oxidative Stress/drug effects
Anti-Inflammatory Agents/pharmacology
Antioxidants/pharmacology
Computer Simulation

@article {pmid41888300,
year = {2026},
author = {Sanchez-Mico, MV and Calvo-Rodriguez, M and Bacskai, BJ},
title = {Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.},
journal = {Nature reviews. Neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41888300},
issn = {1471-0048},
abstract = {Calcium signalling in astrocytes is a fundamental mechanism for maintaining brain homeostasis, shaping neuronal activity, and coordinating vascular and immune responses. Once considered secondary to neuronal signalling, astrocytic Ca[2+] dynamics are now recognized as highly versatile, spatially compartmentalized and essential for regulating neurotransmitter uptake, ion buffering, metabolic support and mitochondrial function. Accumulating evidence shows that these Ca[2+] signalling pathways are progressively remodelled during ageing and become profoundly dysregulated in neurodegenerative diseases, including Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis. Importantly, astrocyte Ca[2+] alterations are heterogeneous and context-dependent, ranging from aberrant spontaneous activity to loss of signalling in specific subcellular domains, reflecting the disease stage, brain region and molecular pathology. Disruption of astrocyte Ca[2+] homeostasis compromises core homeostatic functions and contributes to neuronal vulnerability, circuit dysfunction and impaired neurovascular regulation. By integrating current evidence across physiological, ageing and disease contexts, this Review highlights astrocytic Ca[2+] signalling as a central node in neurodegenerative pathophysiology and underscores its potential as a target for therapeutic intervention.},
}

@article {pmid41890274,
year = {2026},
author = {Silva-Hucha, S and Hernández, RG and Baena-López, D and Fernández de Sevilla, ME and Paradas, C and Morcuende, S},
title = {Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag098},
pmid = {41890274},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis is a complex neurodegenerative disease affecting motor neurons, characterized by the involvement of various factors, including oxidative stress, inflammatory processes, glutamate excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal transport abnormalities, and apoptosis. The complexity of amyotrophic lateral sclerosis arises from its multifactorial aetiology involving diverse genetic, protein, metabolic, and cellular alterations. Mutations of different genes, such as SOD1, C9ORF72, TARDBP, and FUS, have been identified as critical contributors to disease pathophysiology through their facilitation of aberrant protein misfolding and aggregation. All these factors disrupt glutamate homeostasis, leading to calcium-mediated neurotoxicity. Under oxidative stress, motor neurons exhibit a diminished capacity to regulate calcium influx, along with impaired functioning of the mitochondria and endoplasmic reticulum, further compromising cellular integrity. Dysregulation of glutamate signalling also triggers astrocytic stress responses, leading to reduced glutamate clearance, thus worsening neuronal damage through excitotoxic mechanisms. These factors contribute to the excessive production of reactive oxygen species, which exacerbates glutamate imbalance and establishes a detrimental cycle of neuronal damage and glial dysfunction, ultimately intensifying excitotoxicity. This review aims to highlight the role of excitotoxicity in motor neuronal degeneration and to explore the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis. It also examines current therapeutic approaches, including approved treatments and ongoing clinical trials to reduce excitotoxicity, while emphasizing the urgent need for novel, targeted strategies. Given the lack of definitive diagnostic tools and curative therapies, advancing our understanding of the molecular mechanisms driving excitotoxicity and neurodegeneration is, therefore, crucial for the development of more effective, disease-modifying treatments to slow amyotrophic lateral sclerosis progression.},
}

@article {pmid41893050,
year = {2026},
author = {Duranti, E and Villa, C},
title = {Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders.},
journal = {Neurology international},
volume = {18},
number = {3},
pages = {},
pmid = {41893050},
issn = {2035-8385},
abstract = {Cognitive decline represents one of the most common clinical manifestations of neurodegenerative diseases (NDs), substantially affecting the quality of life of both patients and their families. Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are major NDs characterized by a progressive degeneration of the central nervous system, with functional impairments extending beyond motor symptoms to multiple cognitive domains, including memory, attention, language, and executive functions. Increasing evidence highlights misfolded protein accumulation as a key driver of neuronal dysfunction and cognitive deterioration. This narrative review examines the major cognitive deficits associated with these disorders, focusing on the underlying molecular mechanisms, particularly protein aggregation, as well as clinical manifestations and their effects on daily life. Furthermore, current diagnostic tools and emerging therapeutic options for mitigating cognitive decline will be further discussed.},
}

@article {pmid41870813,
year = {2026},
author = {Upadhayay, S},
title = {Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An Insight into Molecular Mechanisms and Therapeutic Approaches.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41870813},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Pentacyclic Triterpenes/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Oxidative Stress/drug effects ; },
abstract = {Neurological disorders represent major public health concerns globally, as they profoundly affect motor function, memory, and cognitive abilities, thus compromising patients' independence and quality of life. Despite extensive research, current treatment approaches predominantly offer palliative care, failing to hinder disease progression. The rising incidence of these disorders underscores an urgent necessity for more efficacious and disease-modifying therapies. According to findings, pentacyclic triterpenoids exhibit neuroprotective properties by inhibiting neuronal oxidative stress, neuroinflammation, apoptosis, and degeneration, making them promising candidates for targeting the underlying causes of neurodegeneration. Therefore, in this review, we explore natural and synthetic pentacyclic triterpenoids that exhibit neuroprotective effects by modulating signaling pathways, such as HMGB1, TLR4, NLRP3, NF-κB, Nrf2, PI3K, Akt, and CREB, which play crucial roles in regulating cell proliferation, differentiation, and neuronal plasticity. The present literature survey is performed by searching various keywords with several combinations: "pentacyclic triterpenes", "neurological disorders", Parkinson's Disease", "Huntington's Disease", "Alzheimer's Disease", "Multiple sclerosis", "Amyotrophic Lateral Sclerosis" "Epilepsy", "mitochondria dysfunction", "oxidative stress", "preclinical studies", "molecular mechanisms", and "clinical studies". Studies indicates that pentacyclic triterpenoids have a wide range of therapeutic potentials, current findings summarizes existing knowledge and examines the neuroprotective properties and potential molecular mechanisms of pentacyclic triterpenoids related with health benefits and neurological diseases. Available evidence suggests that pentacyclic triterpenoids possess the capacity to impede disease progression and may be beneficial in the treatment of neurological disorders. This review strengthens the understanding of pentacyclic triterpenoids and their molecular mechanisms, while also facilitating pharmaceutical discovery and development for neurodegenerative disorders.},
}

Humans
Animals
*Nervous System Diseases/drug therapy/metabolism
*Pentacyclic Triterpenes/therapeutic use/pharmacology
*Neuroprotective Agents/therapeutic use/pharmacology
Signal Transduction/drug effects
Oxidative Stress/drug effects

@article {pmid41872984,
year = {2026},
author = {Toomey, A and Kleinerova, J and Tan, EL and Siah, WF and Bede, P},
title = {Muscle MRI and Muscle Ultrasound Applications in MND/ALS: Academic Insights and Clinical Opportunities.},
journal = {European journal of neurology},
volume = {33},
number = {3},
pages = {e70582},
doi = {10.1111/ene.70582},
pmid = {41872984},
issn = {1468-1331},
support = {HRB JPND-Cofund-2025-3/HRBI_/Health Research Board/Ireland ; JPND-2025"Qual-Bulb-MND"//EU Joint Programme - Neurodegenerative Disease Research/ ; SFI-SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Ultrasonography/methods ; *Muscle, Skeletal/diagnostic imaging ; },
abstract = {BACKGROUND: There is an unmet need for the clinically relevant ALS biomarkers to facilitate an accurate diagnosis in suspected cases, monitor disease progression and evaluate response to therapy in clinical trials. While the MND/ALS literature is dominated by innovative brain studies, motor disability in ALS is primarily driven by neurogenic muscle change impacting mobility, dexterity, respiratory and bulbar function.

METHODS: With the intention of raising awareness of muscle-derived imaging markers in ALS, a systematic review has been conducted. Study designs, imaging methods, data interpretation frameworks, and cohort characteristics were systematically evaluated to identify innovative approaches and barriers to clinical implementation.

RESULTS: A total of 219 studies were screened and 73 original studies selected for systematic review; 37 muscle MRI studies and 36 studies using ultrasound, PET or CT. All of the selected studies successfully captured ALS-associated muscle degeneration and their methods included the evaluation of muscle dimensions (thickness/volumes n = 34), 'acute' denervation (water content, n = 15), fasciculation counts (n = 14), 'chronic' neurogenic change (fat content, n = 21), metabolic changes (n = 4), diffusion alterations (n = 8) and echo intensity changes (n = 13).

CONCLUSIONS: Despite the huge impact of lower motor neuron dysfunction on the patients' independence, survival and quality of life, muscle imaging is a glaringly overlooked frontier of MND/ALS research. This is a missed opportunity, as a variety of non-invasive quantitative muscle imaging techniques have been successfully used in other neurological conditions; these protocols are easy to implement on commercial MRI and ultrasound platforms and recent studies have demonstrated their ease of use and potential clinical utility.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging
*Magnetic Resonance Imaging/methods
Ultrasonography/methods
*Muscle, Skeletal/diagnostic imaging

@article {pmid41877246,
year = {2026},
author = {Shen, R and Sung, K and Ding, J and Wu, C},
title = {Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {41877246},
issn = {2047-9158},
mesh = {Humans ; *Neurodegenerative Diseases/pathology/therapy ; *Axons/pathology ; Animals ; },
abstract = {Axons are unique structural and functional features of nerve cells, which play a critical role in regulating neuronal homeostasis. Dysfunction and degeneration of axons (axonopathy) has been established as an early and prominent contributing mechanism to the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In this review, we briefly summarize the structure and function of axons, and highlight recent advances in the understanding of the role of axons in health and disease. We argue that axons are a potential target for developing novel therapies for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/pathology/therapy
*Axons/pathology
Animals

@article {pmid41881396,
year = {2026},
author = {Zhou, R and Lin, X and Lin, J and Liao, Z and Ni, H and Lin, X and He, Q and Ning, W},
title = {Cellular senescence in neurodegenerative diseases: a bibliometric analysis and mechanistic synthesis linking translational pathways to therapeutic implications.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103110},
doi = {10.1016/j.arr.2026.103110},
pmid = {41881396},
issn = {1872-9649},
abstract = {BACKGROUND: Cellular senescence is now recognized as a pivotal driver of neurodegenerative diseases (NDs). Despite advances in understanding senescence mechanisms, such as the p16[INK4A]/p53-p21[CIP1] pathways and the senescence-associated secretory phenotype (SASP), along with the development of therapeutic strategies like senotherapeutics, the research landscape remains fragmented.

OBJECTIVE: Systematically addresses the fragmentation characterizing current research on cellular senescence in NDs, integrating bibliometric analysis with a mechanistic synthesis of translational relevance and therapeutic implications.

METHODS: A comprehensive bibliometric analysis was performed. Literature retrieval on cellular senescence and four NDs (AD, PD, ALS, HD) was executed in Web of Science Core Collection (WoSCC) on April 30, 2025. CiteSpace V.6.4 R1 and VOSviewer 1.6.20 reconstructed networks for temporal trends, burst detection, and co-occurrence visualization. In addition to bibliometric mapping, we provide a mechanistic synthesis of emerging translational pathways.

RESULTS: Analysis included 269 relevant articles (2002-April 2025). Annual publications and cumulative citations increased markedly since 2018. The US led in output/influence, followed by China and Italy. Key collaborative institutions included Chinese Academy of Sciences, University of Texas System, and University of California System. Leading authors were Lorenz Studer, Judith Campisi, and Julie K. Andersen. Tyler J. Bussian and Peisu Zhang were highly co-cited. Top-cited journals were Nature, PNAS, and PLOS One. Research hotspots focus on abnormal tau protein in senescence and senescent microglia mediating chronic neuroinflammation, development of multi-target senomorphics targeting SASP is emerging as a promising therapeutic direction.

CONCLUSION: Cellular senescence research in NDs (notably AD, PD) shows broad promise from mechanisms to therapy. Future priorities include elucidating tau dysregulation's core role in senescence, developing specific biomarkers and targeted interventions. Senescent microglia are new therapeutic targets. Multi-target senomorphics modulating SASP offer new mechanisms for delaying ND progression. Understanding senescence mechanisms and precise interventions may provide novel ND therapies.},
}

@article {pmid41884172,
year = {2026},
author = {Seki, S and Enomoto, A and Tanaka, S},
title = {The mesencephalic trigeminal neuron: electrophysiological insights into function and dysfunction.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1752701},
pmid = {41884172},
issn = {1662-5102},
abstract = {Mesencephalic trigeminal neurons (MTNs) are the sole primary afferent neurons with cell bodies located within the central nervous system. MTNs convey proprioceptive inputs from masticatory muscles and periodontal ligaments, thereby contributing to the precise regulation of jaw-oral motor functions. Through ionic mechanisms such as currents generated by the voltage-dependent sodium (Nav) channel isoform Nav1.6, hyperpolarization-activated currents, and persistent inward currents, MTNs generate sustained and burst firing that regulate masticatory rhythm and jaw-jerk reflex timing. Their activity is further modulated by neurotransmitters, including serotonin and norepinephrine, which provide flexibility in sensorimotor integration. Pathological conditions such as chronic stress and sodium channel dysfunction induce MTN hyperexcitability or irregular firing, contributing to bruxism, temporomandibular disorders, and feeding impairment in amyotrophic lateral sclerosis models. In addition, aging and tooth loss lead to Piezo2 downregulation and neuronal death, potentially resulting in masticatory dysfunction and cognitive decline. Recent findings suggest that interventions targeting vesicular glutamate transporter 1 projections, melanocortin 4 receptor signaling, and nitric oxide pathways represent novel therapeutic approaches. Taken together, MTNs have emerged as promising targets for treating conditions ranging from masticatory motor disorders to neurodegenerative diseases.},
}

@article {pmid41860208,
year = {2026},
author = {Pirdankar, OH and Nene, AS and Thakur, R and Shah, S and Shenoy, P and Badole, P},
title = {Intravitreal Anti-vascular Endothelial Growth Factor in Retinopathy of Prematurity: A Bibliometric Analysis.},
journal = {Journal of pediatric ophthalmology and strabismus},
volume = {},
number = {},
pages = {1-10},
doi = {10.3928/01913913-20251106-02},
pmid = {41860208},
issn = {1938-2405},
abstract = {Retinopathy of prematurity (ROP) is one of the leading cause of blindness in premature infants. A bibliometric analysis on intravitreal anti-vascular endothelial growth factor (VEGF) in ROP was conducted. A comprehensive search of the article on the Scopus database was conducted with the terms related to "anti-vascular endothelial growth factor and retinopathy of prematurity." Only original research and review articles published in the English language were considered. VOSviewer version 1.6.20 was used for the visualization and analysis of the data. Publication trend, productive countries, researchers' details, commonly cited documents, source and influential journals, and keyword occurrence were analyzed. A total of 329 studies were considered, of which 270 were original articles and 59 were review articles. The highest numbers of publications were seen in the year 2022. The United States, China, Turkey, India, and Taiwan were the top 5 countries that published research on the use of anti-VEGF in ROP. The most documents were published by Wei-Chi Wu (22) and Chi-Chun Lai (14), and Falavarjani et al's article had the most citations (737). A total of 2,504 keywords were identified. All keyword analysis revealed the occurrence of "retinopathy of prematurity" and "human" as a keyword was 290 and 286 times, respectively. Most articles and citations were found in Retina. The use of anti-VEGF in ROP is constantly evolving and bibliometric analysis highlights a research trend and influential authors and journals that have published significant work on it. This article can serve as a guide to conduct a literature review for future researchers.},
}

@article {pmid41863659,
year = {2026},
author = {Mullick, S and Chakraborty, A and Porel, P and Nath, R and Chaudhary, P and Islam, A and Das, J and Pramanik, S and Panigrahy, UP and Sridhar, SB and Mondal, M and Debnath, B and Ashique, S},
title = {Decoding Neuroinflammatory Pathways: The Role of the CXCL12-CXCR4/CXCR7 Axis in ALS-Related Cognitive Impairment.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41863659},
issn = {1559-1182},
mesh = {Humans ; *Chemokine CXCL12/metabolism ; *Receptors, CXCR/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/complications/pathology ; Animals ; *Receptors, CXCR4/metabolism ; *Cognitive Dysfunction/metabolism ; *Signal Transduction/physiology ; *Neuroinflammatory Diseases/metabolism/pathology ; Inflammation/metabolism/pathology ; },
abstract = {Cognitive impairment (CI) and accelerating neuronal deterioration are hallmarks of amyotrophic lateral sclerosis (ALS). Under these circumstances a crucial molecular mechanism in the pathophysiology of CI has been identified: the CXC chemokine receptor type 7 (CXCR7)/CXC chemokine receptor type 4 (CXCR4)/Cysteine-X-cysteine chemokine ligand 12 (CXCL12) region. Research on ALS shows that the CXCR7/CXCR4/CXCL12 complex plays a role in the degeneration of motor neurons and the resulting cognitive decline. JAK/STAT, PI3K/AKT, MAPK, and other signaling pathways are among the ways the axis controls neuronal inflammation, synaptic remodeling, and neuronal maintenance in each of these scenarios. The CXC motif chemokine ligand 12 (CXCL12) and CXC chemokine receptor type 4 (CXCR4) axis is crucial for the start of the inflammatory mechanism because of their function in mediating the chemotaxis of inflammatory cells. By preventing the migration of inflammatory cells via CXCL12 in the inflammatory area, the response to inflammation can be prevented or reduced. Consequently, the development of CXCR4 antagonists has emerged as a cutting-edge strategy for inflammation treatment. Recent research suggests that managing this relationship could reduce cognitive deficits and offer neuroprotective benefits. According to the current review, the CXCL12/CXCR4/CXCR7 pathway may be a promising target for treating cognitive dysfunction in neurodegenerative disorder. It also emphasizes the need for additional research to completely comprehend its function and identify efficient treatments which may result in improved clinical treatment modalities for these debilitating illnesses.},
}

Humans
*Chemokine CXCL12/metabolism
*Receptors, CXCR/metabolism
*Amyotrophic Lateral Sclerosis/metabolism/complications/pathology
Animals
*Receptors, CXCR4/metabolism
*Cognitive Dysfunction/metabolism
*Signal Transduction/physiology
*Neuroinflammatory Diseases/metabolism/pathology
Inflammation/metabolism/pathology

@article {pmid41864543,
year = {2026},
author = {Wu, J and Ma, H and Niu, X and Zhang, Z and Guo, R and Shen, N and Tian, Y and Zhao, H and Yang, Y and Chen, Y},
title = {The p75NTR signaling axis: Bridging neurodevelopmental homeostasis, pathological mechanisms, and therapeutic strategies in neurodegenerative diseases.},
journal = {Ageing research reviews},
volume = {118},
number = {},
pages = {103105},
doi = {10.1016/j.arr.2026.103105},
pmid = {41864543},
issn = {1872-9649},
abstract = {The neurotrophin receptor p75 (p75NTR) plays dual, context-dependent roles in the nervous system that are regulated by ligand binding, co-receptor interactions, and microenvironmental cues. During neurodevelopment, synaptic plasticity, and in neurodegenerative disorders, p75NTR orchestrates opposing cellular responses: it can support neuronal homeostasis through pro-survival pathways, while also initiating apoptotic and inflammatory cascades that exacerbate disease progression. In Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), activation of p75NTR drives pathological processes such as neuronal apoptosis and axonal degeneration, leading to impaired cognitive and motor function.Importantly, different structural domains of p75NTR have divergent effects. The extracellular domain (p75ECD) exhibits neuroprotective properties in AD models, in contrast with the pro-apoptotic activity associated with the full-length receptor. Therapeutic targeting of p75NTR with small-molecule ligands and ROCK inhibitors has shown efficacy in preclinical models, and some candidates have progressed to clinical trials. However, several challenges hinder clinical translation: (1) the mechanisms underlying p75NTR upregulation are not fully understood; (2) its downstream signaling network is highly complex; and (3) existing biomarker systems remain limited.A comprehensive understanding of p75NTR's role in neurodegeneration may clarify pathological mechanisms and reveal novel therapeutic targets. Achieving this will require multidisciplinary collaboration to bridge the gap between basic research and clinical applications.},
}

@article {pmid41866449,
year = {2026},
author = {Wang, Z and He, F and Li, L and Wang, W and Zhang, L and Tang, J and Le, W},
title = {Sleep Disorders in Neurodegenerative Diseases: Pathological Correlations and Underlying Mechanisms.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41866449},
issn = {1995-8218},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), and others, represent an escalating public health burden in aging populations. NDDs are characterized by progressive neuronal loss and misfolded protein aggregation. Despite distinct clinical heterogeneity, these diseases universally present with debilitating non-motor symptoms, among which sleep-wake disorders are highly prevalent. Once considered secondary to neuronal damage, growing evidence now highlights a bidirectional interplay: sleep disruption is not only a consequence of neurodegeneration but also exacerbates its progression. This review synthesizes this complex interplay, outlining sleep phenotypes across major NDDs, dissecting key underlying mechanisms (impaired protein homeostasis, glymphatic dysfunction, chronic neuroinflammation, sleep-regulatory nucleus vulnerability, and circadian dysregulation), and summarizing current pharmacotherapeutic and non-pharmacological interventions. Attenuating sleep disorders may therefore provide symptomatic relief and disease‑modifying effects for NDDs.},
}

@article {pmid41847382,
year = {2026},
author = {Talbot, SR and Scorrano, F and Gaburro, S and Lainee, P and van Gaalen, MM},
title = {From observation to optimization: behavioral metrics that matter in KPI based home cage monitoring.},
journal = {Frontiers in behavioral neuroscience},
volume = {20},
number = {},
pages = {1694689},
pmid = {41847382},
issn = {1662-5153},
abstract = {Most in vivo scientists would agree that digital biomarkers collected via home-cage monitoring generate valuable data. However, few can tell precisely how valuable. The gap between enthusiasm and evidence has slowed the adoption of digital biomarkers in preclinical research. This framework paper addresses that gap by providing explicit key performance indicators (KPIs), organized into scientific, operational, welfare, and financial categories. We show how return-on-investment calculations differ across pharmaceutical companies, contract research organizations (CROs), and academic institutions. Furthermore, we demonstrate the approach through a worked example in an Amyotrophic Lateral Sclerosis (ALS) mouse model that reduces full-time equivalent (FTE) requirements by half. When successfully integrated, digital biomarkers can generate richer datasets, reduce the number of animals, improve welfare, and enhance translational value. However, successful implementation requires clear performance metrics to justify investment and measure success. We also discuss what these technologies cannot do, because understanding limitations matters as much as understanding benefits.},
}

@article {pmid41858792,
year = {2026},
author = {Raber, J and Sharpton, TJ},
title = {Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1771904},
pmid = {41858792},
issn = {1663-4365},
abstract = {The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in germ-free mice demonstrate that microbiome alterations are sufficient to induce cognitive and neuropathological phenotypes, supporting causality in preclinical models. Genetic risk factors and environmental exposures affect both neurodegeneration risk and microbiome composition. In this review, we synthesize evidence from human cohorts and preclinical models on the gut-brain axis in cognitive health and disease. We then present a methodological framework for diet-microbiome-cognition research, addressing causal inference through mediation analysis, supervised approaches for deriving diet scores, validation strategies, and individual heterogeneity. This framework can guide development of microbiome-targeted dietary interventions to improve cognitive outcomes.},
}

@article {pmid41845971,
year = {2026},
author = {Dahlhaus, R and Braun, RJ},
title = {The role of TDP-43 fragments in regular cellular functions and homeostatic failure.},
journal = {Neurobiology of disease},
volume = {222},
number = {},
pages = {107349},
doi = {10.1016/j.nbd.2026.107349},
pmid = {41845971},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons, leading to severe muscle weakness, loss of voluntary movement, and respiratory failure. A widely noted feature of the disease is the presence of TDP-43 proteinopathies. Under homeostatic conditions, the RNA/DNA-binding protein TDP-43 mainly resides in the nucleus, where it functions to regulate gene expression, controlling not only RNA transcription and splicing, but also stability and transport to the cytoplasm. Upon the arrival at ribosomes, TDP-43 may further moderate translation, acting as a global repressor of protein synthesis. However, in over 95% of ALS cases, TDP-43 mislocalises from the nucleus to the cytoplasm, where it enriches in cytoplasmic inclusions that are marked by the presence of misfolded, ubiquitinated, phosphorylated and fragmented protein species of TDP-43. Although recent studies have tried to untangle the relationship between TDP fragments on the one hand, and cytotoxicity as well as neurodegeneration on the other, the results are still a matter of debate. Here, we review our current understanding of the different TDP fragments derived from proteolytic cleavage as well as alternative splicing, addressing the different N-terminal and C-terminal species and evaluating differences in rodent and primate models. We focus our analysis on potential homeostatic functions of TDP fragments in the context of viral infections and myelination control, which could be pivotally interconnected. The findings illustrate several facets of fragmented TDP-43 protein species in scenarios of enhanced cellular stress. Gaining a detailed understanding could help to reveal new treatment options for ALS and other TDP-43 proteinopathies.},
}

@article {pmid41846418,
year = {2026},
author = {Ahire, C and Yadav, R and Bhamare, UU and Kaur, G and Palkar, MB},
title = {From Refractory Epilepsy to Neurodegeneration: Emerging Mechanistic and Clinical Insights Into the Ketogenic Diet.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {6},
pages = {e71609},
doi = {10.1096/fj.202503317R},
pmid = {41846418},
issn = {1530-6860},
mesh = {*Diet, Ketogenic/methods ; Humans ; Animals ; *Neurodegenerative Diseases/diet therapy/metabolism ; *Drug Resistant Epilepsy/diet therapy/metabolism ; },
abstract = {The ketogenic diet (KD), a high-fat, low-carbohydrate intervention, is well established for drug-resistant epilepsy and is increasingly explored in neurodegenerative disorders. KD reduces neuronal hyperexcitability through enhanced γ-aminobutyric acid (GABA)ergic transmission and modulation of neurotransmitter balance, underlying its efficacy in refractory epilepsy. Beyond seizure control, emerging evidence suggests KD may influence disease processes in conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease. Preclinical studies indicate that KD can modulate mitochondrial bioenergetics, oxidative stress, neuroinflammation, neurotransmitter signaling, and gut-brain interactions, though these effects are highly context-dependent and primarily derived from cellular and animal models. Clinical data remain limited, heterogeneous, and short-term, with small cohorts and variable outcome measures. Sustaining adherence and assessing long-term safety remain significant challenges in patient populations. This review summarizes recent experimental and clinical findings, highlighting the molecular and cellular mechanisms through which KD exerts neuroprotective effects. We also evaluate translational evidence and discuss the potential utility of KD as an adjunctive intervention in neurological disease management.},
}

*Diet, Ketogenic/methods
Humans
Animals
*Neurodegenerative Diseases/diet therapy/metabolism
*Drug Resistant Epilepsy/diet therapy/metabolism

@article {pmid41841320,
year = {2026},
author = {El Kaïm, A and Banos, M and Decostre, V and Birnbaum, S and Hogrel, JY and Gargiulo, M},
title = {Sexual health in neuromuscular diseases: Neglected challenges revealed by a scoping review.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602261434092},
doi = {10.1177/22143602261434092},
pmid = {41841320},
issn = {2214-3602},
abstract = {BACKGROUND: Neuromuscular diseases (NMDs) are heterogeneous disorders causing progressive motor decline, multisystem complications, and reduced quality of life. Sexual health, a key component of well-being, remains largely overlooked. This scoping review mapped and synthesized evidence on sexual dysfunction (SD) in adults with NMDs, focusing on prevalence, underlying mechanisms, and research gaps.

METHODS: A systematic search of PubMed, Cochrane Library, and Google Scholar (February-March 2025) identified studies reporting original data on SD in adults with genetically or clinically confirmed NMDs. Citation tracking complemented the search. Data were narratively synthesized following PRISMA-ScR guidelines.

RESULTS: Twenty-seven studies (1983-2024) including 2428 individuals met the inclusion criteria. Most were cross-sectional and questionnaire-based studies. SD was frequent but heterogeneous across conditions. In myotonic dystrophy, erectile dysfunction often related to hypogonadism; in Charcot-Marie-Tooth disease, higher disease severity correlated with altered desire and satisfaction in women; amyloid neuropathies showed autonomic-related erectile and ejaculatory dysfunction in men and multidimensional impairment in women; inflammatory myopathies revealed high SD prevalence in both sexes; amyotrophic lateral sclerosis involved intimacy loss mainly due to disability and psychosocial distress, despite preserved interest; myasthenia gravis displayed SD mainly associated with mental health conditions, X-linked spinal muscular atrophy showed predominantly endocrine-related SD.

CONCLUSION: SD is common, multifactorial, and under-recognized in adults with NMDs. The available evidence remains limited by non-inclusive approaches to sexual orientation and intimacy, scarce physiological assessments, and substantial gaps regarding female sexual health, longitudinal data. Integrating sexual health assessment into routine care for people with NMDs should be prioritized.},
}

@article {pmid41838432,
year = {2026},
author = {Cohen-Salmon, M},
title = {Local Translation in Glial Cells of the Brain.},
journal = {Annual review of cell and developmental biology},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-cellbio-111524-124159},
pmid = {41838432},
issn = {1530-8995},
abstract = {Local protein synthesis is a conserved mechanism that allows cells with intricate architectures to perform compartment-specific functions. By translating messenger RNAs (mRNAs) at distinct subcellular locations, cells can respond swiftly and precisely to localized stimuli. This strategy is crucial in neurons, whose long processes extend far from the cell body. Disruptions in neuronal local translation have been implicated in neurological disorders, including fragile X syndrome, amyotrophic lateral sclerosis, and spinal muscular atrophy. While much of the spotlight has been on neurons, glial cells-microglia, astrocytes, oligodendrocytes, and radial glia-are increasingly recognized for their own dynamic use of local translation. These support cells exhibit asymmetric mRNA localization, suggesting that local protein synthesis plays key roles in their diverse functions. This review explores the emerging landscape of local translation in glial cells and examines how this finely tuned process contributes to both normal brain function and the development of neurological disease.},
}

@article {pmid41837285,
year = {2026},
author = {Gautier, O and Nguyen, TP and Gitler, AD},
title = {Decoding neurodegeneration one cell at a time.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {6},
pages = {},
pmid = {41837285},
issn = {1558-8238},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/pathology/metabolism ; *Single-Cell Analysis ; Animals ; *Neurons/metabolism/pathology ; *Transcriptome ; },
abstract = {Neurodegenerative diseases are characterized by protein misfolding and the selective vulnerability of specific neuronal subtypes. This selective vulnerability presents a paradox; most neurodegenerative disease genes are expressed broadly throughout the brain, and some ubiquitously, but only certain types of neurons are lost while others are resistant. The molecular basis for selective neuronal vulnerability has remained a mystery, but recent genomics technological innovations are starting to provide mechanistic insights. Here, we review how single-cell genomics techniques - single-cell transcriptomics, single-cell epigenomics, and spatial transcriptomics - advance our molecular understanding of selective vulnerability and neurodegeneration across Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington disease. Together, these approaches reveal the cell types affected in disease, define disease-associated molecular states, nominate candidate determinants of vulnerability and degeneration, and situate degenerating neurons within their local tissue context. Continued development and application of these techniques, including single-cell perturbation screens, will expand descriptive atlases of relevant cell types in health and disease and identify causal mechanisms, revealing the molecular basis of vulnerability and degeneration and informing therapeutic development.},
}

Humans
*Neurodegenerative Diseases/genetics/pathology/metabolism
*Single-Cell Analysis
Animals
*Neurons/metabolism/pathology
*Transcriptome

@article {pmid41837791,
year = {2025},
author = {Sahoo, S and Padhy, AA and Shivani, K and Misra, A and Mishra, P},
title = {Ubiquitin signatures on aggregating proteins in neurodegeneration.},
journal = {Essays in biochemistry},
volume = {69},
number = {5},
pages = {},
doi = {10.1042/EBC20253046},
pmid = {41837791},
issn = {1744-1358},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Ubiquitin/metabolism ; Animals ; alpha-Synuclein/metabolism ; Ubiquitination ; Ubiquitin-Protein Ligases/metabolism ; tau Proteins/metabolism ; Protein Aggregates ; },
abstract = {The aberrant accumulation of misfolded proteins marked by cellular dysfunction and progressive neuronal loss is the hallmark of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. This review examines the pivotal role of ubiquitin modifications in altering the fate of aggregation-prone proteins such as tau, α-synuclein, mutant huntingtin, TAR DNA-binding protein 43 and superoxide dismutase 1. The ubiquitin signatures identified by their linkage types, chain architectures and site specificities emerge as a complex regulatory language that influences the clearance, aggregation or cellular propagation of these aggregating proteins. The dysregulation of other components of the ubiquitin association pathways, such as impaired E3 ligases and deubiquitinases, also contributes to the inefficient protein disposal and disease progression. Understanding how ubiquitin signatures alter the spatiotemporal dynamics of aggregating proteins is critical for advancing our knowledge of disease biology. Here, we focus on the role of ubiquitin modifications and their associated regulators affecting protein fate and neurotoxicity, and highlight the current therapeutic strategies targeting the degradation of aggregating proteins to uncover potential avenues for treating neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/metabolism
*Ubiquitin/metabolism
Animals
alpha-Synuclein/metabolism
Ubiquitination
Ubiquitin-Protein Ligases/metabolism
tau Proteins/metabolism
Protein Aggregates

@article {pmid41837283,
year = {2026},
author = {Miller, MR and Dykstra, M and Barmada, S},
title = {Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {6},
pages = {},
pmid = {41837283},
issn = {1558-8238},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Alternative Splicing ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; Protein Isoforms/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative diseases characterized by the nuclear clearance and cytoplasmic aggregation of transactive response DNA/RNA-binding protein of 43 kDa (TDP43). Alternative splicing of TARDBP, the gene encoding TDP43, leads to a surprising diversity of RNA and protein isoforms with unique functions and potential implications for disease pathogenesis. Here, we review the production, properties, and functional consequences of alternative splicing in the development of ALS and FTD, focusing primarily on TDP43 due to its integral connection with the pathogenesis of sporadic as well as familial forms of these diseases. We synthesize current evidence on the biology of alternative TARDBP splicing, highlight key questions regarding its role in TDP43 proteinopathies such as ALS and FTD, and touch on the larger phenomenon of alternative splicing and its relationship to disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Frontotemporal Dementia/genetics/metabolism/pathology
*Alternative Splicing
*DNA-Binding Proteins/genetics/metabolism
Animals
Protein Isoforms/genetics

@article {pmid41833275,
year = {2026},
author = {Yang, Z and Xu, Q and Yang, X and Zhou, T and Xiong, Y and Liu, Y and Li, D and Wu, H},
title = {The role of zinc transporter 1 (ZnT1) in health and disease: From molecular mechanisms to therapeutic opportunities.},
journal = {European journal of medicinal chemistry},
volume = {309},
number = {},
pages = {118727},
doi = {10.1016/j.ejmech.2026.118727},
pmid = {41833275},
issn = {1768-3254},
abstract = {Zinc transporter 1 (ZnT1/SLC30A1) is a major plasma membrane-localized zinc efflux transporter and acts as a central regulator of cellular metal homeostasis. Beyond exporting Zn[2+], recent evidence reveals that ZnT1 also transports Cu[2+] and serves as a molecular hub linking zinc-copper interplay, redox balance, immune signaling and programmed cell death. This review summarizes current advances in ZnT1 structure, transport mechanism, regulatory networks and physiological roles across the gut-liver-immune-neuro-cardiovascular axis. We further outline its pathological involvement in Wilson disease, amyotrophic lateral sclerosis, cancer and inflammatory disorders, highlighting ferroptosis, cuproptosis and metabolic reprogramming as key downstream consequences of ZnT1 dysregulation. Emerging therapeutic approaches include small-molecule modulators, RNA-based regulation, antibody targeting and metal-based interventions. Although challenges remain-such as tissue specificity, systemic toxicity and biomarker development-ZnT1 is rapidly evolving from a basic transport protein to a promising precision medicine target. Continued efforts in structural biology, single-cell metallomics and targeted delivery systems will accelerate its clinical translation.},
}

@article {pmid41833626,
year = {2026},
author = {Sedighi, S and Guan, T and Michetti, F and Cordani, M and Behrooz, AB and Sabouni, F and Eshraghi, M and Saleem, A and Ghavami, S and Aghanoori, MR},
title = {Autophagy-exosome crosstalk in neurodegeneration: Mechanisms and therapeutic opportunities.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {109025},
doi = {10.1016/j.pharmthera.2026.109025},
pmid = {41833626},
issn = {1879-016X},
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and multiple sclerosis, share a common pathogenic signature: disrupted proteostasis driven by impaired autophagy and maladaptive exosome dynamics. Under normal conditions, autophagy maintains neuronal homeostasis by clearing misfolded proteins and damaged organelles, while exosomes mediate neuroglial communication. When autophagic flux is impaired or lysosomal function is compromised, intracellular cargo handling can shift toward secretion, and undegraded cargo may be redirected into exosomes/EVs, which disseminate pathogenic proteins such as amyloid-β, tau, α-synuclein, and TDP-43, a phenomenon reported in several experimental models and proposed to contribute to intercellular spread of pathology. This dual dysregulation amplifies neuroinflammation, demyelination, and progressive neuronal loss. Pharmacological strategies aimed at restoring the autophagy exosome axis are gaining traction. Agents such as rapamycin and resveratrol enhance autophagic flux, whereas engineered or stem-cell-derived exosomes delivering siRNAs, neurotrophic factors, or anti-inflammatory microRNAs show promise in preclinical neuroprotection and immune modulation. However, translational barriers remain, including safety, biodistribution, dosing, and standardization. Emerging artificial intelligence (AI) and machine learning (ML) frameworks can accelerate translation by integrating multi-omics and exosomal biomarker datasets for early diagnosis, patient stratification, and therapy optimization. Deep learning and generative modeling may further enable rational drug design to fine-tune autophagy and engineer targeted exosome delivery to the brain. Collectively, these advances position the autophagy-exosome axis as an integrative framework linking intracellular clearance with intercellular signaling, with emerging diagnostic and therapeutic implications for neurodegenerative disorders.},
}

@article {pmid41836534,
year = {2026},
author = {Scirocco, E and Paganoni, S and Brizzi, K},
title = {Approaching Serious Illness Conversations in Amyotrophic Lateral Sclerosis Using Telehealth: A Practical Guide.},
journal = {Neurology. Clinical practice},
volume = {16},
number = {2},
pages = {e200600},
pmid = {41836534},
issn = {2163-0402},
abstract = {PURPOSE OF REVIEW: Given the lack of consensus on serious illness conversations (SIC) in amyotrophic lateral sclerosis (ALS) by using telehealth, we aim to provide practical strategies in this setting.

RECENT FINDINGS: Over the past 5 years, there has been substantial growth in telehealth, especially after the global COVID-19 pandemic. In ALS, telehealth has become an increasingly used tool for providing clinical care, especially as the disease progresses, when travel becomes challenging and geographic constraints arise. As ALS advances, clinicians often have SIC with individuals living with ALS and their caregivers using telehealth. In the literature, few recommendations are available to improve telehealth communication in the neuropalliative setting.

SUMMARY: We present 3 case scenarios showcasing telehealth strategies for SICs, with specific considerations for individuals living with ALS. We provide a strategy, CARE in ALS, to support telehealth communication in individuals with speech impairments. We hope to provide practical guidance for health care clinicians in this specific setting.},
}

@article {pmid41827910,
year = {2026},
author = {Manganelli, F and Perfetto, C and Carletta, O and Gerbino, V},
title = {TBK1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: Mechanistic Insights into Impaired Autophagy and Proteostatic Failure.},
journal = {Cells},
volume = {15},
number = {5},
pages = {},
pmid = {41827910},
issn = {2073-4409},
support = {GR-2021-12375436//Italian Ministry of Health/ ; MotorTBK1//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; },
mesh = {Humans ; *Frontotemporal Dementia/genetics/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Autophagy/genetics ; *Protein Serine-Threonine Kinases/genetics/metabolism ; *Mutation/genetics ; Animals ; *Proteostasis/genetics ; Lysosomes/metabolism ; },
abstract = {Mutations in the TANK-binding kinase 1 (TBK1) gene represent a significant genetic link across the Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) spectrum. As a multifunctional serine/threonine kinase, TBK1 serves as a central orchestrator of the autophagy-lysosome pathway, regulating critical stages from initial cargo recognition and autophagosome biogenesis to vesicle maturation and lysosomal fusion. This review examines the mechanisms by which TBK1 coordinates these diverse autophagic functions. We then focus on how ALS/FTD-associated mutations-ranging from truncating variants causing haploinsufficiency to domain-specific missense mutations-disrupt these essential processes.},
}

Humans
*Frontotemporal Dementia/genetics/pathology
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Autophagy/genetics
*Protein Serine-Threonine Kinases/genetics/metabolism
*Mutation/genetics
Animals
*Proteostasis/genetics
Lysosomes/metabolism

@article {pmid41831326,
year = {2026},
author = {Furlan, R and Di Sapio, A and Ferraro, D and Rossi, E and Valentino, P and Terracciano, D},
title = {Translating neurofilament light chain testing into clinical practice: a multidisciplinary implementation roadmap.},
journal = {Clinical chemistry and laboratory medicine},
volume = {},
number = {},
pages = {},
pmid = {41831326},
issn = {1437-4331},
abstract = {Neurofilament light chain (NfL) has been identified as a sensitive and broadly validated biomarker of neuroaxonal injury across multiple neurological conditions, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and atypical parkinsonian syndromes. This position paper provides a multidisciplinary roadmap for translating circulating NfL testing into routine clinical practice, integrating analytical, interpretative, and organizational dimensions. It summarizes the biological basis and clinical evidence supporting NfL as a diagnostic, prognostic, and monitoring tool, emphasizing its high sensitivity to neuroaxonal injury across both acute inflammatory and chronic degenerative processes. Comparative analysis of immunoassay technologies identifies strengths and critical sources of variability, while operational guidelines highlight the need for pre-analytical standardization, inter-laboratory harmonization, and participation in quality control schemes. Confounders such as age, BMI, renal function, and comorbidities are shown to significantly influence interpretation, supporting the use of age-adjusted Z-scores, percentiles, and longitudinal normalization for accurate patient-level evaluation. From a clinical standpoint, the paper focuses on practical indications for NfL testing in MS, recommending its use for disease activity prediction and monitoring, treatment decisions and treatment response assessment. Integration of blood NfL with magnetic resonance imaging (MRI), glial fibrillary acidic protein (GFAP) and other biomarkers measurement is proposed as a core strategy for biomarker-driven precision neurology. The authors outline an implementation model encompassing laboratory validation, structured reporting and alignment with national neurological care pathways. They conclude that the transition of NfL into clinical use requires harmonized analytical procedures, interdisciplinary education, and sustainable governance frameworks. Priority actions include regulatory qualification, establishment of international reference materials, and development of pragmatic real-world trials to consolidate its clinical utility. When these measures are achieved, NfL will represent a cornerstone biomarker for precision neurology and neurodegeneration monitoring.},
}

@article {pmid41276980,
year = {2026},
author = {Patel, K and Sarathamani, T and Kothandasamy, K and Sethy, PK and Behera, SK and Nanthaamornphong, A},
title = {Computational Approaches to Neurological Disorder Diagnosis: An In-Depth Review of Current Methods and Future Prospects.},
journal = {Current medical imaging},
volume = {22},
number = {},
pages = {e15734056404224},
doi = {10.2174/0115734056404224251026110800},
pmid = {41276980},
issn = {1573-4056},
mesh = {Humans ; *Nervous System Diseases/diagnostic imaging/diagnosis ; Neuroimaging/methods ; Machine Learning ; *Diagnosis, Computer-Assisted/methods ; Artificial Intelligence ; },
abstract = {The rapid advancement of computational technologies has significantly transformed medical diagnostics, particularly in the realm of neurological disorders. This review provides a comprehensive analysis of the current computational approaches employed for the diagnosis of five major neurological disorders: Alzheimer's disease, Parkinson's disease, Epilepsy, Huntington's disease, and Amyotrophic Lateral Sclerosis. By evaluating 140 peer-reviewed studies, we explored a diverse array of diagnostic methods, including machine learning algorithms, neuroimaging techniques, and electrophysiological signal analysis. Our review highlights the efficacy, accuracy, and limitations of these diagnostic methods, emphasizing their role in early detection and differential diagnosis. Furthermore, we discuss the integration of multimodal data and the potential of emerging technologies such as deep learning and artificial intelligence to enhance diagnostic practices. We also address the current challenges in clinical implementation and propose future research directions to improve diagnostic precision and patient outcomes. This review aims to serve as a valuable resource for researchers, clinicians, and stakeholders in the field of neurodiagnostics, fostering a deeper understanding of computational methodologies that shape the future of neurological disorder diagnosis.},
}

Humans
*Nervous System Diseases/diagnostic imaging/diagnosis
Neuroimaging/methods
Machine Learning
*Diagnosis, Computer-Assisted/methods
Artificial Intelligence

@article {pmid41817655,
year = {2026},
author = {Bakshi, V and Pathak, B and Majie, A and Ghosh, A and Gupta, A and Jain, N and Pandey, M and Nair, AB and Jacob, S and Mazumder, PM and Sharma, N and Kumari, N and Gorain, B},
title = {Advancement in therapeutic application of quantum dots in amyotrophic lateral sclerosis: current opportunities and challenges.},
journal = {Drug delivery and translational research},
volume = {},
number = {},
pages = {},
pmid = {41817655},
issn = {2190-3948},
abstract = {Despite advancements in healthcare settings in developed countries, the early detection and higher mortality rate associated with amyotrophic lateral sclerosis (ALS), a fatal motor neuronal disorder, remain challenging. Recently, quantum dots (QDs) have emerged as a promising nanocarrier in the prognosis and treatment of ALS owing to their unique multifunctional properties. QDs, through their photoluminescence properties upon excitation, can facilitate the identification and real-time monitoring of disease biomarkers. They also act as a nanocarrier for the targeted delivery of therapeutics, avoiding accumulation at the non-targeted sites and minimising toxicity. QDs can be fabricated to conjugate with protein biomarkers linked to ALS, such as specific proteins, nucleic acids, or genetic variants, for the diagnosis of the disease. Such fabrication could lead to enhanced identification and diagnostic patterns of ALS, thereby contributing to improved therapeutic intervention strategies. Furthermore, these tiny structures could be applied in combined biosensor formats to identify ALS-associated biomarkers in body fluids, which would be a highly sensitive diagnostic system. Subsequently, comprehensive multiomics techniques have demonstrated improved identification of newer protein targets associated with neurological complications. Overall, QDs can be explored as a potential tool to identify biomarkers relevant to ALS, diagnose the disease at its early stages, and track the effectiveness of the treatment. The integration of QD with omic-based strategies and network analysis can potentially catalyse a breakthrough in the management of ALS. Therefore, this review aims to explore the application of QDs in ALS diagnosis and management, advancements in research, clinical trials, and patents.},
}

@article {pmid41821014,
year = {2026},
author = {Sligar, C and Sluyter, R and Ooi, L},
title = {Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03764-9},
pmid = {41821014},
issn = {1742-2094},
support = {AL210095//U.S. Department of Defense/ ; CE230100021//Australian Research Council Centre of Excellence in Quantum Biotechnology/ ; },
}

@article {pmid41823531,
year = {2026},
author = {Chen, W and Tian, H and Wei, R and Chen, X and Jia, Y},
title = {Ferritin in ferroptosis: Implications for neurodegenerative diseases (Review).},
journal = {International journal of molecular medicine},
volume = {57},
number = {5},
pages = {},
pmid = {41823531},
issn = {1791-244X},
mesh = {Humans ; *Ferroptosis ; *Neurodegenerative Diseases/metabolism/pathology ; *Ferritins/metabolism ; Iron/metabolism ; Animals ; Homeostasis ; Biomarkers/metabolism ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive loss of neurons. Although the precise pathogenesis of such diseases is complex and multifactorial, several molecular pathways have been implicated, including the aggregation of misfolded proteins, mitochondrial dysfunction, oxidative stress, neuroinflammation and disrupted iron homeostasis. Emerging evidence has underscored the pivotal role of ferroptosis, an iron‑dependent, non‑apoptotic form of cell death, in neurodegenerative disease progression. Ferritin, characterized by a 24‑subunit hollow sphere structure composed of heavy and light chains, plays a key role in the network regulating cerebral iron homeostasis. In response to cellular iron overload, ferritin expression is upregulated to sequester labile iron and mitigate Fenton reaction‑mediated toxicity, thus exerting a cytoprotective function. Paradoxically, ferritin can be degraded via ferritinophagy, a selective autophagic process that releases toxic ferrous iron and directly triggers ferroptosis. This review systematically reviews the role of ferritin within the iron homeostasis network to elucidate the connection between the dysregulation of iron metabolism and the pathological mechanisms of neurodegenerative diseases. The study focused on the potential role of ferritin as a biomarker for early diagnosis, therapeutic strategies targeting ferritin pathways to restore iron homeostasis and the clinical translational value of magnetic resonance imaging‑based non‑invasive quantification of cerebral iron deposition. It is crucial to elucidate the multidimensional roles of ferritin in neurodegeneration to provide a theoretical foundation for precision diagnostic and therapeutic approaches.},
}

Humans
*Ferroptosis
*Neurodegenerative Diseases/metabolism/pathology
*Ferritins/metabolism
Iron/metabolism
Animals
Homeostasis
Biomarkers/metabolism

@article {pmid41825541,
year = {2026},
author = {Pan, HL and Ge, JY and Zhang, ZA and Xu, JH and Wu, JN and Ju, Y and Zhang, XY and Jiang, ZJ and Chen, Y and Xu, YZ and Liu, XJ},
title = {The role of MyD88 in the nervous system: Neuronal functions, implications in neurological diseases, and therapeutic potential.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {109016},
doi = {10.1016/j.pharmthera.2026.109016},
pmid = {41825541},
issn = {1879-016X},
abstract = {Myeloid differentiation primary response 88 (MyD88), a central adaptor protein governing Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling cascades, is increasingly recognized as a pivotal mediator of neuroimmune interactions and neuromodulation. Beyond its canonical immune functions, emerging evidence reveals widespread MyD88 expression throughout the nervous system, where it plays functional roles in both glial populations and neuronal networks. While previous reviews have largely focused on glial mechanisms, recent studies highlight a complex, often overlooked aspect: the dual role of neuronal MyD88 signaling in orchestrating neurodevelopment while paradoxically driving neuroinflammation and synaptic dysregulation. Given the growing interest in innate immunity's involvement in central nervous system (CNS) diseases, a timely synthesis of MyD88 biology-from molecular mechanisms to therapeutic implications-is essential to bridge the fields of immunology and neuroscience. This article provides a comprehensive review of MyD88, synthesizing contemporary insights into its multifaceted regulatory roles in neural homeostasis and pathogenesis. We place particular emphasis on its mechanistic contributions to brain injury, chronic pain, and neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Furthermore, we evaluate innovative therapeutic approaches targeting MyD88-dependent pathways, highlighting recent pharmacotherapeutic advances and their neuroprotective potential. Finally, addressing the limitations of current strategies, we advocate for a new framework focused on developing therapeutics with increased cell selectivity, thereby advancing the precision and translational potential of MyD88-targeted interventions.},
}

@article {pmid41826709,
year = {2026},
author = {Jones, CT and Hill, ER},
title = {The evolution of speech communication devices for anarthria: a review.},
journal = {Journal of neurology},
volume = {273},
number = {3},
pages = {},
pmid = {41826709},
issn = {1432-1459},
mesh = {Humans ; *Communication Devices for People with Disabilities/trends ; *Facial Paralysis/rehabilitation/etiology ; *Communication Disorders/etiology ; },
abstract = {Anarthria is a lack of verbal communication caused by physiological disturbances in the motor pathway. While affected individuals retain the ability to comprehend and produce speech, orofacial paralysis renders them unable to execute speech. Anarthria can be caused by amyotrophic lateral sclerosis, stroke, traumatic brain injury, and other etiologies that affect the descending motor pathway. A wide range of technologies has been developed and tested to improve communication efficiency for patients with anarthria and accompanying paralysis. This review evaluates three key eras of communication device development. First, before implantation devices gained traction, many communication devices revolved around blinks, head and eye tracking, and non-invasive brain recording. Second, implanted cortical neuroprosthetics were designed to improve accuracy and speed of communication. Finally, the review analyzes the future era, where accessibility, patient comfort, and broader applications of neural analysis elevate communication for patients with anarthria to match fluid communication. Restoring speech communication in patients with anarthria is vital to improve their quality of life. Therefore, understanding communication device efficiency and its future trajectory is of utmost clinical importance.},
}

Humans
*Communication Devices for People with Disabilities/trends
*Facial Paralysis/rehabilitation/etiology
*Communication Disorders/etiology

@article {pmid41813136,
year = {2026},
author = {Perry, CM and Martin, DDO},
title = {ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {46},
number = {10},
pages = {},
pmid = {41813136},
issn = {1529-2401},
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Huntington Disease/metabolism/genetics/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Huntingtin Protein/metabolism/genetics ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are lethal neurodegenerative diseases affecting motor function. Though their etiology and pathology are distinct, recent evidence suggests commonalities between TAR DNA-binding protein (TDP-43), which is associated with 97% of ALS cases, and huntingtin (HTT), the causative protein of HD. ALS is a heterogeneous, lethal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, as well as brainstem and spinal cord degeneration. The causes of ALS are complex, variable, and, in some cases, unknown, but most cases involve mislocalization of the protein TDP-43. In contrast, HD is a monogenic, autosomal dominant, lethal neurodegenerative disease caused by polyglutamine expansion in HTT protein and characterized by the progressive loss of neurons in the brain, particularly in the striatum, which results in motor, cognitive, and behavioral changes. Although HD is not typically associated with motor neuron loss, recent evidence suggests a link between HTT and TDP-43 within the context of both ALS and HD, as well as links to related neurodegenerative diseases, such as frontotemporal dementia (FTD) and spinocerebellar ataxia type 2 (SCA2). Herein, we discuss confirmed cases of concurrent ALS and HD and the overlap of underlying disease mechanisms that potentially contribute to the onset and progression of these two devastating neurodegenerative diseases, with a focus on commonalities between TDP-43 and HTT. We propose that elucidating these commonalities will aid in the identification of broad-spectrum disease risk factors and potential overlapping treatment targets.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*Huntington Disease/metabolism/genetics/pathology
*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
*Huntingtin Protein/metabolism/genetics
Animals

@article {pmid41814918,
year = {2026},
author = {Banfi, P and Dimabuyu-Francisco, M and Nicolini, A and Compalati, E and Lax, A and Volpato, E and Garuti, G and Leonardi, G and Bach, JR and Solidoro, P},
title = {Non-invasive ventilation support during feeding tube placement in amyotrophic lateral sclerosis patients with moderate to severe ventilatory impairment: an update.},
journal = {Panminerva medica},
volume = {68},
number = {1},
pages = {10-18},
doi = {10.23736/S0031-0808.26.05313-9},
pmid = {41814918},
issn = {1827-1898},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications/physiopathology ; *Noninvasive Ventilation/adverse effects/methods ; *Enteral Nutrition/adverse effects/methods ; *Gastrostomy/adverse effects/methods ; *Respiratory Insufficiency/therapy/physiopathology/etiology/diagnosis ; Treatment Outcome ; Quality of Life ; *Intubation, Gastrointestinal/adverse effects ; Severity of Illness Index ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration, leading to muscle weakness and respiratory issues. Enteral nutrition is used in ALS patients when they experience severe weight loss, dysphagia, dehydration, or a risk of aspiration pneumonia. Noninvasive ventilation (NIV) is essential for managing respiratory failure in ALS patients, especially during feeding tube placement procedures. This narrative review compares percutaneous endoscopic gastrostomy (PEG), percutaneous radiologic gastrostomy (PRG), and radiologically inserted G-tube (RIG) in ALS patients receiving NIV. Studies were found through electronic database searches of Medline and Embase from 2000 to June 2025, including the Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO Online Research Database, and Scopus. The main outcome was the occurrence of adverse events during and within thirty days after gastrostomy tube placement in NIV. Eleven studies involving NIV during PEG/RIG procedures were included. NIV during PEG, RIG, or PRG placement seems to be safe for ALS patients, with few adverse events reported, though future studies with higher methodological quality are needed. Additionally, the review highlights the benefits of better nutritional support, improved quality of life, interdisciplinary teamwork, increased survival rates, and personalized care.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications/physiopathology
*Noninvasive Ventilation/adverse effects/methods
*Enteral Nutrition/adverse effects/methods
*Gastrostomy/adverse effects/methods
*Respiratory Insufficiency/therapy/physiopathology/etiology/diagnosis
Treatment Outcome
Quality of Life
*Intubation, Gastrointestinal/adverse effects
Severity of Illness Index

@article {pmid41809632,
year = {2026},
author = {Mazurek, CY and Kaniuk, JK and Ahuja, CS},
title = {Mesenchymal stem cells and the central nervous system: historical perspectives and future directions.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1742864},
pmid = {41809632},
issn = {1662-5099},
abstract = {Mesenchymal stem cells (MSCs) have been studied as a potential therapy for a wide range of conditions for approximately 30 years. MSCs have shown promise in treating pathologies of or affecting the central nervous system (CNS), specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), traumatic brain injury (TBI), degenerative disc disease (DDD), and sepsis/meningitis. The therapeutic benefits of MSCs derive primarily from their arsenal of secreted factors that promote anti-inflammatory and pro-survival pathways while attenuating harmful immune responses, thus making them powerful immunomodulatory entities which are also capable of affecting a diverse range of cellular functions to promote endogenous mechanisms of repair. This review summarizes the current state of clinical trials research regarding pathologies of the CNS with a focus on historical progression and upcoming trials. We take a mechanistic approach to explain the therapeutic basis of MSCs and how this has informed clinical trials. We also mention the role of the MSC secretome and MSC exosomes in the treatment of CNS pathologies as well as their increasing use in clinical trials. Finally, we address the challenges inherent to the clinical translation and implementation of MSC therapies along with future directions of the field.},
}

@article {pmid41804522,
year = {2026},
author = {Fujita, K and Matsui, N and Izumi, Y},
title = {[Immune Cells and Proteins Associated with Disease Progression in Amyotrophic Lateral Sclerosis: New Insights from Multiomics Analyses].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {3},
pages = {285-288},
doi = {10.11477/mf.188160960780030285},
pmid = {41804522},
issn = {1881-6096},
mesh = {*Amyotrophic Lateral Sclerosis/immunology/genetics ; Humans ; Disease Progression ; Proteomics ; Cytokines ; Multiomics ; },
abstract = {Disease progression in amyotrophic lateral sclerosis shows substantial individual variability, and immune mechanisms have attracted attention as underlying factors. Immune profiles associated with disease progression were identified using cytokine profiling, proteomics, and single-cell analyses. Peripheral blood mononuclear cells, such as Th17 cells and effector CD8+ T cells, along with inflammation-related proteins, including interleukin-17A and CD94, are associated with disease progression. This review summarizes the findings of multi-omics studies.},
}

*Amyotrophic Lateral Sclerosis/immunology/genetics
Humans
Disease Progression
Proteomics
Cytokines
Multiomics

@article {pmid41794640,
year = {2026},
author = {Chen, X and Zhu, B},
title = {Decoding the functions of nuclear speckles in neurodegeneration.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.01.010},
pmid = {41794640},
issn = {1878-108X},
support = {DP2 GM140924/GM/NIGMS NIH HHS/United States ; R35 GM157978/GM/NIGMS NIH HHS/United States ; },
abstract = {Nuclear speckles, traditionally considered mainly as reservoirs of splicing factors, are increasingly recognized as dynamic biomolecular condensates essential for RNA metabolism, transcriptional regulation, and chromatin organization. Recent advances reveal their phase separation properties, compositional complexity, and stress-responsive remodeling, positioning nuclear speckles as key regulators of proteostasis and stress adaptation. Here, we synthesize emerging evidence linking nuclear speckle dysfunction to neurodegenerative proteinopathies, particularly amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and tauopathies. We highlight how disease-associated repeat RNAs, dipeptide repeat proteins, and hyperphosphorylated tau disrupt nuclear speckle integrity, driving transcriptional and splicing defects. Finally, we discuss therapeutic strategies to rejuvenate nuclear speckles, emphasizing their potential as novel targets for restoring proteostasis and mitigating neurodegeneration. This review underscores nuclear speckles as critical yet underexplored regulators of neuronal resilience.},
}

@article {pmid41791963,
year = {2026},
author = {Mendon, A and Jain, S and Mishra, N and Bagwe Parab, S},
title = {Calprotectin as an immune-dysregulation biomarker in amyotrophic lateral sclerosis: Insights for diagnosis and therapy.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2026.02.148},
pmid = {41791963},
issn = {0035-3787},
abstract = {Motor neuron degeneration is a defining feature of amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disorder. Early diagnosis remains challenging due to the absence of reliable and validated biomarkers. Calprotectin, a well-established inflammatory marker in various neuroinflammatory conditions, has paradoxically been found at reduced levels in the blood of ALS patients in a limited number of studies, raising the hypothesis of immune dysregulation rather than classical neuroinflammation. However, these findings are primarily derived from small patient cohorts and have yet to be independently replicated. This review critically assesses the emerging role of calprotectin in ALS by comparing it with other candidate biomarkers, including vascular endothelial growth factor (VEGF), apolipoprotein A1 (ApoA1), interleukin-8 (IL-8), interleukin-7 (IL-7), and interleukin-10 (IL-10). While calprotectin may reflect a distinct immunological profile, its standalone diagnostic value remains unclear. Nonetheless, its integration into a multi-analyte biomarker panel could enhance diagnostic precision and biological insight. The review also explores underlying immunological mechanisms, including receptor interactions (RAGE, TLR4, CD33), cellular mediators (microglia, lymphocytes, monocytes), and therapeutic implications. Future research should prioritize mechanistic investigation of calprotectin modulation in ALS, longitudinal validation in larger cohorts, and integration within multimodal biomarker frameworks. A better understanding of disease-specific immune alterations may contribute to earlier diagnosis, stratified patient monitoring, and targeted therapeutic development.},
}

@article {pmid41788548,
year = {2026},
author = {Zheng, Y and Zhou, W and Chang, H and Zheng, K},
title = {Brain organoids as precision models for neurodegenerative diseases: from disease modeling to drug discovery.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1764964},
pmid = {41788548},
issn = {1662-4548},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR-Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges-including insufficient maturation, lack of vascularization and immune components, and batch variability-the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)-driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.},
}

@article {pmid41785403,
year = {2026},
author = {Oh, J and Oh, SI},
title = {Subjective sleep quality in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/21678421.2026.2614597},
pmid = {41785403},
issn = {2167-9223},
abstract = {OBJECTIVE: Sleep disturbances are common and clinically significant non-motor symptoms in amyotrophic lateral sclerosis (ALS), arising from motor, respiratory, and psychological factors. This study aimed to synthesize available evidence on subjective sleep quality in ALS, estimate the prevalence of poor sleep quality, examine associated factors, and compare patients with healthy controls.

METHODS: : PubMed, EMBASE, Cochrane Central, and CINAHL were searched for studies published between January 2000 and August 2025 that assessed subjective sleep quality in ALS using validated patient-reported outcome measures, such as Pittsburgh Sleep Quality Index (PSQI). Pooled analyses were performed using random-effects models. Meta-regression was applied to explore associations with demographic and clinical variables.

RESULTS: : A total of 23 studies comprising 1899 ALS patients were included, of which 20 were eligible for meta-analysis. All included studies assessed subjective sleep quality using the PSQI, and the pooled mean PSQI score was 6.94, exceeding the clinical cutoff for poor sleep quality. The pooled prevalence of poor sleepers was 56.7%. Nine studies including healthy controls showed significantly higher PSQI scores in ALS patients compared with controls (mean difference 2.69). Several factors, including functional status, depression, anxiety, fatigue, daytime sleepiness, constipation, and cognitive impairment, were associated with poorer sleep, however, meta-regression did not identify significant associations with age, sex, disease duration, or ALSFRS-R.

CONCLUSIONS: : Sleep disturbances are highly prevalent and clinically significant in ALS. These findings highlight the need for systematic screening and proactive management across all stages of the disease. Future research should evaluate a wider range of interventions to improve sleep quality and patient outcomes.},
}

@article {pmid41784486,
year = {2026},
author = {Calix Kannaley, K},
title = {Exploring the use of narrative-based approaches in individuals with amyotrophic lateral sclerosis: A narrative review.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e81},
doi = {10.1017/S1478951526101965},
pmid = {41784486},
issn = {1478-9523},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications/therapy ; *Narration ; Adaptation, Psychological ; Qualitative Research ; },
abstract = {OBJECTIVES: Narrative-based approaches have been utilized in medicine to better understand the illness experiences of individuals living with chronic conditions. In particular, people with amyotrophic lateral sclerosis (pALS) may benefit from use of narrative-based approaches, given the potential impact of progressive decline on identity of self. This review explores the use of narrative-based approaches in studies involving pALS to provide further insight to the experiences and psychosocial needs of this population.

METHODS: A search was conducted utilizing EMBASE, CINAHL, PsycInfo, and Google Scholar with several terms related to amyotrophic lateral sclerosis (ALS) and narrative-based approaches. Studies were included if they were written in English, incorporated methods that promoted the production of narratives, and reported data that could be clearly isolated to pALS.

RESULTS: The search revealed a total of 154 articles for title and abstract screening. Fifty-two articles were selected for full-text review. Thirty-two articles met the criteria for data extraction. Four descriptive categories emerged upon examination of the narrative-based approaches implemented across the studies: psychosocial intervention, illness experience, intervention targeting specific needs, and secondary analysis of data. Some of the common themes identified across studies included: loss of physical and communicative function, adaptation to life changes, shifts in identity, and tension with the healthcare system.

SIGNIFICANCE OF RESULTS: Despite the communication challenges that often coincide with disease progression, narrative-based approaches can be utilized in pALS. These approaches should be implemented to gain insight on the disease experiences of pALS, providing opportunity for patient-centered interventions to address the psychosocial needs of this population.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/complications/therapy
*Narration
Adaptation, Psychological
Qualitative Research

@article {pmid41783572,
year = {2026},
author = {Liu, W and Xue, Y and Cao, C and Yang, L and Zhang, L},
title = {Copper Homeostasis and Cuproptosis in Neurological Disorders.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {580005},
pmid = {41783572},
issn = {1177-8881},
mesh = {*Copper/metabolism ; Humans ; *Homeostasis ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) pose a serious global public health threat, with complex etiologies involving genetic, environmental, and metabolic factors. Current data indicate that the prevalence of these disorders is rapidly increasing with the aging population, resulting in a growing economic and healthcare burden worldwide. In recent years, the imbalance of copper homeostasis has been increasingly implicated in the pathogenesis of neurological diseases. Copper overload can aggravate neuronal injury by inducing oxidative stress (OS), mitochondrial dysfunction, and protein misfolding, while copper deficiency disrupts the function of copper-dependent enzymes and leads to metabolic abnormalities. The mechanism of cuproptosis, proposed in 2022, describes a novel form of programmed cell death characterized by lipoylated protein aggregation and the loss of Fe-S cluster proteins, offering new insights into copper-related diseases. Multiple studies have demonstrated the crucial role of copper homeostasis and cuproptosis in the onset, progression, and treatment of neurological diseases. This narrative review summarizes the molecular mechanisms involved in copper homeostasis regulation and, on that basis, discusses the role of copper metabolism abnormalities in AD, PD, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Wilson's disease (WD), Menkes disease (MD), and stroke. Additionally, we highlight the mechanisms of existing copper-regulating drugs and their therapeutic potential in neurological disorders, while pointing out the limitations of current drug development.},
}

*Copper/metabolism
Humans
*Homeostasis
*Nervous System Diseases/metabolism/drug therapy
Animals

@article {pmid41783158,
year = {2025},
author = {Uemura, K and Hiro, S and Attachaipanich, S and Du, R and Yusof, NISM and Kinoshita, M and Hikosaka, M and Ohtsuki, G},
title = {Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1669272},
pmid = {41783158},
issn = {1662-5102},
abstract = {In this review, we synthesize recent conceptual and experimental advances in neuroscience, highlighting selected studies that delineate the roles of reactive microglia and astrocytes in the contexts of developmental inflammatory stress, neurodegenerative diseases, and cellular senescence. Since the characterization of disease-associated glial phenotypes in 2017, building on earlier pioneering discoveries, we focus here on disease-associated microglia (DAM) and disease-associated astrocyte (DAA) to reassess their contributions to glio-inflammation. It is now recognized that the stress-induced glial states are far from uniform; however, the ontogeny, molecular determinants, and functional consequences of this heterogeneity remain incompletely understood, particularly in psychiatric disorders, Alzheimer's disease, and amyotrophic lateral sclerosis. Accordingly, we compare the glial heterogeneity and its underlying mechanisms across translational mouse models and human neuropathology, considering their evolutionary and physiological contexts. While this review does not aim to be exhaustive, we propose an integrative framework that redefines glial stress responses through the combined lenses of inflammation, transcriptomics, mitochondrial dynamics, lipid metabolism, epigenomic regulation, and cellular senescence. Finally, we outline emerging frontiers for AI-enabled multi-omic physiological and pathological approaches, emphasizing their potential to illuminate glial state transitions and accelerate therapeutic discovery in the near future.},
}

@article {pmid37132107,
year = {2023},
author = {Alameri, AA and Ghanni, MU and Ali, A and Singh, M and Al-Gazally, ME and Almulla, AF and Alexis Ramírez-Coronel, A and Mustafa, YF and Gupta, R and Obaid, RF and Gabr, GA and Farhood, B},
title = {The Effects of Curcumin on Astrocytes in Common Neurodegenerative Conditions.},
journal = {Mini reviews in medicinal chemistry},
volume = {23},
number = {22},
pages = {2117-2129},
doi = {10.2174/1389557523666230502143131},
pmid = {37132107},
issn = {1875-5607},
mesh = {*Curcumin/pharmacology/chemistry/therapeutic use ; Humans ; *Astrocytes/drug effects/metabolism/pathology ; *Neurodegenerative Diseases/drug therapy/pathology/metabolism ; Animals ; *Neuroprotective Agents/pharmacology/chemistry ; },
abstract = {Neurodegenerative diseases are age-related, multifactorial, and complicated conditions that affect the nervous system. In most cases, these diseases may begin with an accumulation of misfolded proteins rather than decay before they develop clinical symptoms. The progression of these diseases can be influenced by a number of internal and external factors, including oxidative damage, neuro-inflammation, and the accumulation of misfolded amyloid proteins. Astrocytes, with the highest abundance among the cells of the mammalian central nervous system, perform several important activities, such as maintaining brain homeostasis and playing a role in the neurodegenerative condition onset and progress. Therefore, these cells have been considered to be potential targets for managing neurodegeneration. Curcumin, with multiple special properties, has been effectively prescribed to manage various diseases. It has hepato-protective, anti-carcinogenic, cardio-protective, thrombo-suppressive, anti-inflammatory, chemo-therapeutic, anti-arthritic, chemo-preventive, and anti-oxidant activities. In the current review, the effects of curcumin on astrocytes in common neurodegenerative conditions, such as Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are discussed. Hence, it can be concluded that astrocytes play a critical role in neurodegenerative diseases, and curcumin is able to directly modulate astrocyte activity in neurodegenerative diseases.},
}

*Curcumin/pharmacology/chemistry/therapeutic use
Humans
*Astrocytes/drug effects/metabolism/pathology
*Neurodegenerative Diseases/drug therapy/pathology/metabolism
Animals
*Neuroprotective Agents/pharmacology/chemistry

@article {pmid41782322,
year = {2026},
author = {Kaya, Y and Kırboğa, KK},
title = {Brain Organoids as Emerging Platforms for Modeling Neurodegenerative Diseases: Progress, Challenges, and Future Directions.},
journal = {Journal of neurochemistry},
volume = {170},
number = {3},
pages = {e70395},
doi = {10.1111/jnc.70395},
pmid = {41782322},
issn = {1471-4159},
mesh = {Humans ; *Organoids/pathology/metabolism ; *Neurodegenerative Diseases/pathology/metabolism ; *Brain/pathology/metabolism ; Animals ; Induced Pluripotent Stem Cells ; },
abstract = {Neurodegenerative diseases are a group of disorders (such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis) characterized by loss of function and death of neurons in different parts of the nervous system. These pathologies constitute a global burden, especially for aging populations. This circumstance leads to an increasing demand for understanding the fundamental mechanisms and development of therapeutic strategies. Conventional models, including two-dimensional cell culture and animal models, postmortem brain tissue provide an overview about neurodegenerative disorders but do not completely recapitulate cellular and molecular mechanisms of the human brain. Although three-dimensional (3D) brain organoids exhibit similar properties with physiological and pathological conditions of human brain, including interaction of neuronal, glial cells and self-organizing structure, protein aggregation, neuroinflammation, and neuronal degeneration. The integration of reprogrammed human induced pluripotent stem cells (iPSCs) with 3D brain organoid systems provides a clinical platform as a bridge between bench to bedside. Brain organoids have been used to elucidate novel insights into the molecular and genetic mechanisms underlying neurodegenerative diseases. Furthermore, brain organoids serve as a tool for in vitro disease modeling, drug screening and emergence of new treatments. Despite these clinical benefits, there are various limitations such as incomplete tissue maturation, lack of vascularization and incomplete cellular diversity in this 3D culture system. This review describes in detail the advantages and disadvantages of brain organoids usage in modeling neurodegenerative diseases from a contemporary perspective.},
}

Humans
*Organoids/pathology/metabolism
*Neurodegenerative Diseases/pathology/metabolism
*Brain/pathology/metabolism
Animals
Induced Pluripotent Stem Cells

@article {pmid37632964,
year = {2023},
author = {Wang, T and Yang, X and Du, R and Zheng, S and Cui, H},
title = {Acupuncture in the Treatment of Amyotrophic Lateral Sclerosis: A Research Progress in Clinical Trials.},
journal = {Alternative therapies in health and medicine},
volume = {29},
number = {7},
pages = {114-118},
pmid = {37632964},
issn = {1078-6791},
mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Acupuncture Therapy/methods ; Quality of Life ; Clinical Trials as Topic ; },
abstract = {BACKGROUND: Acupuncture, a complementary and alternative medicine (CAM) modality, shows promise as an integrative therapy for Amyotrophic Lateral Sclerosis (ALS) due to the chronic nature of the disease and its persistent symptoms. Many patients turn to CAM for ALS treatment.

OBJECTIVE: This review assesses acupuncture's efficacy in treating Amyotrophic Lateral Sclerosis.

METHODS: We searched China National Knowledge Network (CNKI) and PubMed databases for Chinese and English articles, including clinical trials, case studies, cohorts, and randomized controlled trials. The search, performed on March 31, 2023, encompassed literature published up to that date. Keywords used in titles and abstracts were (acupuncture) OR (electro-acupuncture)) AND (Amyotrophic Lateral Sclerosis).

RESULTS: Among the 45 articles studied, 34 were included in this research. Acupuncture's benefits primarily lie in neuro-immune system regulation, enhanced quality of life, reduced fatigue, disease progression delay, and fewer relapses.

CONCLUSIONS: Recent clinical trials highlight the potential of traditional Chinese acupuncture in improving Amyotrophic Lateral Sclerosis symptoms (e.g., fatigue, neural functional deficits) and curtailing relapses. Consequently, acupuncture holds promise as an integrative therapy for ALS patients.},
}

*Amyotrophic Lateral Sclerosis/therapy
Humans
*Acupuncture Therapy/methods
Quality of Life
Clinical Trials as Topic

@article {pmid32029539,
year = {2020},
author = {Turner, MR and Barohn, RJ and Corcia, P and Fink, JK and Harms, MB and Kiernan, MC and Ravits, J and Silani, V and Simmons, Z and Statland, J and van den Berg, LH and , and Mitsumoto, H},
title = {Primary lateral sclerosis: consensus diagnostic criteria.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {91},
number = {4},
pages = {373-377},
pmid = {32029539},
issn = {1468-330X},
support = {R01 AG062268/AG/NIA NIH HHS/United States ; R01 MH120794/MH/NIMH NIH HHS/United States ; R13 NS111790/NS/NINDS NIH HHS/United States ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; Consensus ; Delayed Diagnosis ; Diagnosis, Differential ; *Motor Neuron Disease/diagnosis/pathology ; *Motor Neurons/pathology ; },
abstract = {Primary lateral sclerosis (PLS) is a neurodegenerative disorder of the adult motor system. Characterised by a slowly progressive upper motor neuron syndrome, the diagnosis is clinical, after exclusion of structural, neurodegenerative and metabolic mimics. Differentiation of PLS from upper motor neuron-predominant forms of amyotrophic lateral sclerosis remains a significant challenge in the early symptomatic phase of both disorders, with ongoing debate as to whether they form a clinical and histopathological continuum. Current diagnostic criteria for PLS may be a barrier to therapeutic development, requiring long delays between symptom onset and formal diagnosis. While new technologies sensitive to both upper and lower motor neuron involvement may ultimately resolve controversies in the diagnosis of PLS, we present updated consensus diagnostic criteria with the aim of reducing diagnostic delay, optimising therapeutic trial design and catalysing the development of disease-modifying therapy.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/pathology
Consensus
Delayed Diagnosis
Diagnosis, Differential
*Motor Neuron Disease/diagnosis/pathology
*Motor Neurons/pathology

@article {pmid41781371,
year = {2026},
author = {Zhang, L and Huang, Y and Huang, W and Huang, Q and Lin, Y and Gu, J},
title = {TDP-43 phosphorylation: Exploring kinases, phosphatases, and therapeutic potential in neurodegeneration.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424284},
doi = {10.1177/13872877261424284},
pmid = {41781371},
issn = {1875-8908},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a multifunctional DNA/RNA-binding protein whose abnormal phosphorylation and aggregation are central to the pathogenesis of several neurodegenerative diseases. TDP-43 proteinopathy, characterized by hyperphosphorylation and cytoplasmic accumulation, is a defining pathological feature of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and is frequently observed in Alzheimer's disease. The phosphorylation state of TDP-43 is dynamically regulated by a network of protein kinases-including CK1, GSK3β, CDC7, and PKA-and counterbalanced by phosphatases such as PP2A and PP1; however, the precise molecular mechanisms governing this equilibrium in disease remain incompletely understood. Notably, phosphorylated TDP-43 acquires prion-like properties, enabling self-templated aggregation and cell-to-cell propagation, which amplifies pathology and drives disease progression. These insights have catalyzed the development of therapeutic strategies aimed at modulating TDP-43 phosphorylation, with kinase inhibitors and phosphatase enhancers emerging as promising candidates for targeting TDP-43 proteinopathies. This review integrates current knowledge on the regulatory networks controlling TDP-43 phosphorylation, examines its role in prion-like spread, and evaluates emerging therapeutic approaches aimed at mitigating TDP-43-mediated neurodegeneration.},
}

@article {pmid41777232,
year = {2026},
author = {Yerraguntla, S and Bakshi, B and Chandran, K and Foucher, J and Benatar, M and Wicks, P and Bedlack, R and Shirilla, D and Sun, Y and Maragakis, N and Greenstein, E and Mascias Cadavid, J and Rao, A and Allen, O and Dyckman, K and Wang, O and Beauchamp, M and Chang, V and Brown, A and Carbunar, O and Paganoni, S and Bertorini, T and Pioro, E and Elsharif, B and Jiang, N and Pattee, G and Carter, G and Breevoort, S and Tito, E and Nathaniel, G and Jackson, C and Olby, N and McDermott, C and Ratner, D and Li, X},
title = {ALSUntangled #82: N-acetylcysteine.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2026.2638590},
pmid = {41777232},
issn = {2167-9223},
abstract = {N-acetylcysteine is a thiol-containing compound and a precursor of glutathione, with mechanistic plausibility for ALS, including reducing oxidative stress, regulating neuroinflammation, and mitigating mitochondrial dysfunction. Preclinical studies have yielded conflicting results on whether N-acetylcysteine can delay the onset of motor impairment and prolong survival in ALS mouse models. Several case studies of oral or subcutaneous administration of N-acetylcysteine in patients with ALS did not demonstrate convincing benefits. Clinical trials to date have also failed to demonstrate efficacy in slowing ALS progression. While N-acetylcysteine shows theoretical promise, further research is needed to clarify its therapeutic role in ALS. At present, ALSUntangled does not support the use of N-acetylcysteine as a treatment to slow ALS progression.},
}

@article {pmid41653702,
year = {2026},
author = {Sebastianelli, L and Versace, V and Ferrazzoli, D and Ortelli, P and Trinka, E and Sellner, J and Nardone, R},
title = {Neurophysiology in the mirror: A tri-layer model of mirror movements informed by TMS evidence.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {184},
number = {},
pages = {2111692},
doi = {10.1016/j.clinph.2026.2111692},
pmid = {41653702},
issn = {1872-8952},
mesh = {Humans ; *Transcranial Magnetic Stimulation/methods ; *Movement Disorders/physiopathology ; Evoked Potentials, Motor/physiology ; *Motor Cortex/physiopathology/physiology ; Movement/physiology ; Pyramidal Tracts/physiopathology/physiology ; },
abstract = {OBJECTIVE: Mirror movements are involuntary, task-coupled contractions in contralateral homologous muscles during unilateral movement. While often described as a developmental remnant or rare clinical sign, mirror movements offer insight into the physiological mechanisms that underlie motor lateralization and interhemispheric balance. This review aimed to synthesize the available neurophysiological evidence-primarily from transcranial magnetic stimulation (TMS)-and propose a structured, mechanism-based framework for interpreting mirror movements across neurological conditions.

METHODS: A structured narrative review was conducted of studies published between 1966 and November 2025 using TMS in individuals with congenital, developmental, or acquired mirror movements. Studies using neuroimaging or peripheral electrophysiology were included selectively to support anatomical or functional interpretation of TMS findings. Data were organized into three mechanistic layers based on prevailing neurophysiological signatures rather than etiology alone.

RESULTS: Three non-mutually exclusive mechanisms were identified: (I) persistent fast-conducting ipsilateral corticospinal projections, primarily in congenital mirror movement syndromes and early brain injury; (II) deficient transcallosal inhibition, observed in conditions affecting interhemispheric balance such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and callosal agenesis; and (III) bilateral overactivation of premotor and supplementary motor areas, especially under conditions of impaired motor program selection or increased task demands.

CONCLUSIONS: Mirror movements can be interpreted within a tri-layer model reflecting distinct disruptions in corticospinal connectivity, interhemispheric inhibition, and supraspinal motor control.

SIGNIFICANCE: This framework provides an integrative model for interpreting neurophysiological findings in mirror movements, offering insight into hierarchical motor control without implying specific diagnostic or therapeutic applications.},
}

Humans
*Transcranial Magnetic Stimulation/methods
*Movement Disorders/physiopathology
Evoked Potentials, Motor/physiology
*Motor Cortex/physiopathology/physiology
Movement/physiology
Pyramidal Tracts/physiopathology/physiology

@article {pmid41502663,
year = {2025},
author = {Ma, Y and Tian, H and Xiao, W and Ma, Y and Su, H and Zhu, L and Jiang, Y and Ge, L and Li, Y and Yuan, M and Liu, X},
title = {Machine Learning Approaches for Optimizing Drug Combinations in Neurodegenerative Diseases: A Brief Review.},
journal = {ACS omega},
volume = {10},
number = {48},
pages = {57950-57973},
pmid = {41502663},
issn = {2470-1343},
abstract = {As the global population ages, the prevalence of neurodegenerative diseases (NDDs)(?)including Alzheimer's disease, Parkinson's disease, Huntington's disease, Multisystem Atrophy (multiple system atrophy), and amyotrophic lateral sclerosis(?)continues to rise, largely driven by environmental, metabolic, and lifestyle risk factors. Advances in computational technologies, particularly machine learning (ML) and deep learning, are reshaping research in this field. This review summarizes the major features of these diseases and emphasizes the role of ML in drug discovery, virtual screening, drug repurposing, and drug combination optimization. Representative approaches include support vector machines for classification, convolutional neural networks|convolutional neural network for imaging analysis, recurrent neural networks for temporal biomedical data, and transformers for multimodal integration. These methods highlight the potential of computational strategies to improve therapeutic development. In addition, the review underscores the substantial incidence rates and socioeconomic burden of these conditions, which have made them focal points for algorithmic innovation. With research evolving rapidly, the development of AI-driven approaches is expected to enable more effective, targeted interventions and improve patient outcomes. This Perspective provides a concise overview of current progress and identifies promising future directions in the fight against NDDs.},
}

@article {pmid41775321,
year = {2026},
author = {Lu, YH and Zhu, XP and Li, S and Zhang, FN and Cai, CB and Tian, M and Zhu, YH and Zeng, LH and Tan, J and Yu, CY and Chen, J},
title = {From scaffold to effector: reframing GFAP in neurodegeneration.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.02.051},
pmid = {41775321},
issn = {2090-1224},
abstract = {BACKGROUND: Neurodegenerative disorders impose a growing global burden, yet disease-modifying therapies remain limited. Glial fibrillary acidic protein (GFAP) has shifted from a passive astrocytic marker to an active effector that shapes neurodegenerative pathology.

AIM: of Review: This review synthesizes mechanistic and translational evidence that defines GFAP as a proteoform-governed hub and highlights its value for biomarker-guided precision intervention. Key Scientific Concepts of Review: An extensive literature search across major databases was conducted using predefined keywords and strict inclusion criteria, covering mechanistic, pathological, and clinical studies. Evidence supports a GFAP proteoform code in which alternative splicing generates functionally distinct isoforms, and PTMs encode context-dependent assembly dynamics and signaling outputs. We summarize how GFAP proteoforms integrate cytoskeletal remodeling with inflammatory transcriptional programs (notably STAT3 and NF-κB), proteostasis stress, and mitochondrial dysfunction, thereby coupling astrocyte state transitions to neuronal vulnerability and synaptic impairment. Disease trajectories are context-specific: GFAP dysfunction drives primary toxicity in Alexander disease (AxD); in Alzheimer's disease (AD), isoform-specific mechanisms intersect with amyloidogenic machinery and track early preclinical astrocyte activation; and in frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), GFAP reflects inflammatory-metabolic coupling during progression. Translationally, ultrasensitive plasma assays reveal GFAP elevation years to decades before symptom onset, complementing NfL and amyloid/tau within AT(N)-oriented diagnostic frameworks. Therapeutically, we evaluate precision strategies beyond global suppression, including ASO-based modulation, targeting STAT3/NF-κB-driven reactive programs, and restoring proteostasis via chaperone/autophagy pathways. Future progress hinges on isoform-/PTM-specific probes, conformational sensors, and spatial proteomic atlases validated in prospective longitudinal cohorts. In conclusion, GFAP represents both a mechanistic driver and a scalable biomarker, offering a translationally actionable axis to advance precision medicine in neurodegeneration.},
}

@article {pmid41455589,
year = {2026},
author = {Ruiz-Ortiz, M and Esteban-Pérez, J and Gómez-Grande, A and Martínez-Albero, E and Benito-León, J},
title = {Motor band sign in [18]F-FDG PET/CT studies: a biomarker of degenerative upper motor neuron disease? A study of three cases and literature review.},
journal = {Neurologia},
volume = {41},
number = {2},
pages = {501931},
doi = {10.1016/j.nrleng.2025.501931},
pmid = {41455589},
issn = {2173-5808},
mesh = {Humans ; *Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; *Motor Neuron Disease/diagnostic imaging ; Male ; Middle Aged ; Female ; Aged ; Biomarkers ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; Radiopharmaceuticals ; },
abstract = {INTRODUCTION: Motor neuron diseases (MND) encompass conditions like amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), marked by progressive degeneration of upper and/or lower motor neurons. The identification of specific biomarkers is crucial to reduce diagnostic delays.

METHODS: This study presents three clinical cases evaluated at the Hospital Universitario 12 de Octubre, where the motor band sign on brain 18 F-FDG PET/CT aided the diagnosis of MND. The studies were conducted using a SIEMENS Biograph True Point 6, with a review of relevant literature.

RESULTS: In all three patients, PET/CT revealed hypometabolism in the prerolandic region, indicative of the motor band sign, contributing to the diagnosis of PLS or ALS.

DISCUSSION: The motor band sign on 18F-FDG PET/CT emerges as a potential marker of upper motor neuron involvement, though the heterogeneity of MNDs and variability across studies call for further research to establish its specificity and sensitivity.

CONCLUSION: The motor band sign on 18F-FDG PET/CT is a promising biomarker for MNDs, although further studies are required to confirm its diagnostic validity.},
}

Humans
*Positron Emission Tomography Computed Tomography
Fluorodeoxyglucose F18
*Motor Neuron Disease/diagnostic imaging
Male
Middle Aged
Female
Aged
Biomarkers
Amyotrophic Lateral Sclerosis/diagnostic imaging
Radiopharmaceuticals

@article {pmid40708508,
year = {2026},
author = {Rana, A and Malviya, R and Rajput, S and Sridhar, SB and Wadhwa, T},
title = {Trends in Nanoparticle-based Strategies for the Management of Neuroinflammation.},
journal = {CNS & neurological disorders drug targets},
volume = {25},
number = {1},
pages = {39-55},
pmid = {40708508},
issn = {1996-3181},
mesh = {Humans ; *Neuroinflammatory Diseases/drug therapy ; Animals ; *Nanoparticles/therapeutic use ; *Drug Delivery Systems/methods ; *Neurodegenerative Diseases/drug therapy ; Blood-Brain Barrier/drug effects ; Microglia/drug effects ; },
abstract = {Neuroinflammation, characterised by an overactive immune system in the brain and spinal cord, has now been tied to several neurodegenerative diseases. Here, immune cells invade into the brain, activating astrocytes and microglia. Neuroinflammation is a common symptom of many neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This inflammatory reaction occurs within the central nervous system (CNS). Neurological dysfunction results from the inflammatory response, which arises in reaction to any kind of brain injury. Regulating neuroinflammation can be useful for controlling brain disorders associated with neuroinflammation. Several targeted drug delivery systems attempt to treat neuroinflammation caused by neurodegenerative illnesses or brain tumours by targeting the microglia and other immune cells in the central nervous system. Therefore, biodegradable and biocompatible NPs (nanoparticles) could be developed as a treatment for neurodegenerative diseases caused by neuroinflammation or as a less invasive means of transporting other drugs across the blood-brain barrier. Numerous applications of gold nanoparticles (AuNPs) in the treatment of neurological diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are studied in this article. To prevent neuroinflammation and microglia over-activation, some NPs have recently been found to be effective anti-inflammatory medication carriers that cross the blood-brain barrier.},
}

Humans
*Neuroinflammatory Diseases/drug therapy
Animals
*Nanoparticles/therapeutic use
*Drug Delivery Systems/methods
*Neurodegenerative Diseases/drug therapy
Blood-Brain Barrier/drug effects
Microglia/drug effects

@article {pmid40103545,
year = {2026},
author = {Sonaglioni, A and Torretta, P and Nicolosi, GL and Lombardo, M},
title = {Left ventricular mechanics assessment in amyloidosis patients: a systematic review and meta-analysis.},
journal = {Minerva cardiology and angiology},
volume = {74},
number = {1},
pages = {60-74},
doi = {10.23736/S2724-5683.24.06683-3},
pmid = {40103545},
issn = {2724-5772},
mesh = {Humans ; *Amyloidosis/physiopathology/diagnostic imaging/complications ; Echocardiography/methods ; *Ventricular Dysfunction, Left/diagnostic imaging/physiopathology/etiology ; Ventricular Function, Left ; Magnetic Resonance Imaging/methods ; Heart Ventricles/diagnostic imaging/physiopathology ; },
abstract = {BACKGROUND: Over the last decade, a small number of studies have used speckle tracking echocardiography (STE) or cardiac magnetic resonance (CMR) for measuring left ventricular (LV) mechanics in patients with amyloidosis. This systematic review and meta-analysis aimed at assessing the overall influence of amyloidosis on LV global longitudinal strain (GLS) and regional longitudinal strain at basal (BLS), mid (MLS) and apical (ALS) level, respectively.

METHODS: All imaging studies assessing LV-GLS, LV-BLS, LV-MLS and LV-ALS in amyloidosis patients versus healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LV-GLS, LV-BLS, LV-MLS and LV-ALS) were pooled as a standardized mean differences (SMDs) comparing amyloidosis group with healthy controls. The overall SMDs of LV-GLS, LV-BLS, LV-MLS and LV-ALS were calculated using the random-effect model.

RESULTS: The full-texts of 13 studies with 553 amyloidosis patients and 575 healthy controls were analyzed. STE (53.8%) and CMR (46.2%) studies were separately analyzed. Average LV-GLS magnitude was significantly impaired in amyloidosis patients vs. controls in both STE (13.8±3.9 vs. 19.8±2.7%) and CMR (12.3±4 vs. 17.9±3.5%) studies. The impairment of segmental strain detected in amyloidosis patients was prevalent at basal and mid level, with relative "apical sparing." SMDs obtained for LV-GLS (SMD -1.80, 95% CI: -2.35, -1.24, P <0.001), LV-BLS (-1.98; 95% CI: -2.51, -1.45, P <0.001) and LV-MLS (-1.84; 95% CI: -2.46, -1.23, P <0.001) assessment were significantly larger than that obtained for LV-ALS (-0.72; 95% CI: -1.31, -0.13, P=0.02) measurement. Substantial heterogeneity was found among the studies assessing LV-GLS (I[2]=92.5%), LV-BLS (I[2]=91.4%), LV-MLS (I[2]=94.3%) and LV-ALS (I[2]=94.6%). Egger's test yielded a P value of 0.10, 0.20, 0.09 and 0.55 for LV-GLS, LV-BLS, LV-MLS and LV-ALS assessment respectively, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for LV-GLS, LV-BLS, LV-MLS and LV-ALS (all P<0.05).

CONCLUSIONS: Amyloidosis has a large negative effect on LV-GLS, primarily related to the deterioration of segmental longitudinal strain at the basal and mid level, with relative apical sparing.},
}

Humans
*Amyloidosis/physiopathology/diagnostic imaging/complications
Echocardiography/methods
*Ventricular Dysfunction, Left/diagnostic imaging/physiopathology/etiology
Ventricular Function, Left
Magnetic Resonance Imaging/methods
Heart Ventricles/diagnostic imaging/physiopathology

@article {pmid41772759,
year = {2026},
author = {Donega, S and Gorospe, M and Harries, LW and Ferrucci, L},
title = {Loss of Splicing Homeostasis as a Hallmark of Aging.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/10985549.2026.2627235},
pmid = {41772759},
issn = {1098-5549},
abstract = {Alternative splicing is a fundamental mechanism that ensures accurate gene expression, supports cellular adaptability, and expands protein diversity beyond the limits of a fixed gene pool. With aging, splicing fidelity weakens, contributing to decline in RNA homeostasis and disrupting essential cellular functions, including mitochondrial oxidative phosphorylation, genome stability, and immune regulation, and in turn accelerating tissue and organ dysfunction. Evidence from senescent cells, aged tissues, and model organisms shows that altered levels of splicing factors and increased RNA polymerase II elongation rates impair co-transcriptional splicing and promote mis-spliced isoforms that reinforce senescence and drive pathology. Dysfunction of RNA-binding proteins further contributes to aberrant splicing, linking splicing defects to age-related diseases such as atherosclerosis, osteoarthritis, sarcopenia, and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Therapeutic strategies to correct splicing defects, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, ADAR-mediated editing, and RNA aptamers, can restore a homeostatic balance of mRNA isoforms. However, major challenges remain, including distinguishing adaptive physiological from pathological splicing 'noise' and achieving targeted delivery to tissues. Despite these obstacles, RNA splicing dysregulation represents a promising avenue to extend health span by reestablishing homeostatic RNA programs, and reinforces the idea that "transcriptomic instability" is a hallmark of aging.},
}

@article {pmid41772317,
year = {2026},
author = {Weller, B and Lin, CW and Rothballer, S and Calderwood, MA and Falter-Braun, P and Falter, C},
title = {NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.},
journal = {Journal of neurovirology},
volume = {32},
number = {2},
pages = {},
pmid = {41772317},
issn = {1538-2443},
mesh = {Humans ; *Neurodegenerative Diseases/virology/genetics/pathology ; *Host-Pathogen Interactions/genetics ; *Viral Proteins/genetics/metabolism ; *Open Reading Frames/genetics ; Animals ; Virus Replication/genetics ; },
abstract = {Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neurological symptoms or by triggering immune responses resulting in neuropathology. Nevertheless, systematic studies of the direct interplay between viral and host proteins in neurodegeneration remain scarce. A key aspect of viral pathogenesis is direct interaction between viral and host proteins (protein-protein interactions, PPIs), which are essential for viral replication and can disrupt or redirect host cell function Kim et al. (Nat Biotechnol, 2022); Zhou et al. (Res Sq, 2022), potentially contributing to the development of diseases traditionally considered non-communicable. Understanding these molecular mechanisms is crucial for advancing diagnostic and therapeutic strategies in neurodegenerative conditions, particularly ALS and MS. To enable systematic studies of these interactions, we introduce NeuroViOme as ORFeome resource encompassing nearly all protein-coding sequences from nine viruses selected based on their prevalence, neurotropism, and mechanistic or epidemiological links to neurodegenerative processes. NeuroViOme includes ORFs from Enteroviruses (EV-A71, EV-D68, CVB3, Echovirus E30), Herpesviruses (HSV-1, EBV, HHV3/Varicella Zoster), the endogenous retrovirus HERV-K, and Polyomavirus JCPyV. To our knowledge, this represents the most comprehensive viral ORF set assembled for neurodegeneration research to date. The collection builds the foundation for interactome mapping and functional genomics analyses and provides a valuable basis for systematic studies of viral perturbations of host pathways.},
}

Humans
*Neurodegenerative Diseases/virology/genetics/pathology
*Host-Pathogen Interactions/genetics
*Viral Proteins/genetics/metabolism
*Open Reading Frames/genetics
Animals
Virus Replication/genetics

@article {pmid41765421,
year = {2026},
author = {Niidome, T and Ishida, T},
title = {[Mechanism of action and clinical trial results of a new drug for amyotrophic lateral sclerosis (ALS), Mecobalamin (Rozebalamin[®]) for intramuscular injection, 25 mg].},
journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
volume = {161},
number = {2},
pages = {115-122},
doi = {10.1254/fpj.25066},
pmid = {41765421},
issn = {0015-5691},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Vitamin B 12/administration & dosage/analogs & derivatives/therapeutic use/pharmacology ; Injections, Intramuscular ; Animals ; Clinical Trials as Topic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, intractable neurodegenerative disease characterized by generalized muscle atrophy and weakness, dysarthria, dysphagia, and respiratory muscle paralysis. Respiratory dysfunction due to muscle weakness is the primary cause of death; without mechanical ventilation, death typically occurs within 2 to 5 years after onset. Mecobalamin, an active form of vitamin B12, is thought to suppress homocysteine-induced neuronal cell death in ALS by acting as a coenzyme for methionine synthase, which catalyzes the conversion of homocysteine to methionine. Since the 1990s, research on neurodegenerative diseases supported by Japan's Ministry of Health, Labour and Welfare has suggested that high-dose mecobalamin may confer clinical benefits in ALS. This led to the initiation of clinical development. A Phase II/III double-blind, placebo-controlled comparative trial was conducted, but did not meet its primary endpoint. Based on these trial findings, an investigator-initiated Phase III placebo-controlled, double-blind comparative trial was conducted primarily at Tokushima University Hospital, targeting patients who developed ALS within one year before starting the trial. The trial demonstrated the efficacy of high-dose mecobalamin in slowing the decline in the Revised ALS Functional Rating Scale total score, which was the primary endpoint. Safety was also confirmed. Based on these results, mecobalamin received regulatory approval in September 2024 for the indication "slowing the progression of functional impairment in ALS." It is expected to offer a new treatment option for patients with ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy
Humans
*Vitamin B 12/administration & dosage/analogs & derivatives/therapeutic use/pharmacology
Injections, Intramuscular
Animals
Clinical Trials as Topic

@article {pmid41764146,
year = {2026},
author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R},
title = {Neuroinflammation and Oxidative Stress in SOD1 Animal Models of ALS: A Meta-analysis Study of Their Effects on Disease Onset and Progression.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41764146},
issn = {1559-1182},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Oxidative Stress/physiology ; Disease Models, Animal ; *Disease Progression ; *Superoxide Dismutase-1/metabolism ; *Neuroinflammatory Diseases/pathology ; Humans ; Mice ; *Inflammation/pathology ; Male ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disorder characterized by progressive motor neuron degeneration. Among the key mechanisms implicated in ALS pathogenesis, neuroinflammation and oxidative stress have emerged as prominent contributors to disease progression. This systematic review with meta-analysis involved 344 preclinical studies conducted on SOD1 animal models of ALS, to quantitatively evaluate the effects of treatments targeting neuroinflammation and oxidative stress on functional outcomes such as disease onset, survival, motor neuron degeneration, and locomotion. Data extraction and validation were performed using a combination of a large language model and human review. Results show that while most interventions led to reduced astrogliosis, M1 microgliosis, and oxidative stress, and increased M2 microgliosis, these effects were more strongly associated with improved survival and motor outcomes than with delayed disease onset. The analysis also revealed that treatment timing significantly influences outcomes, with interventions initiated during the late pre-onset window showing the highest efficacy. Furthermore, sex differences were noted, with male mice displaying better outcomes in progression metrics but worse in the age at onset. Overall, this meta-analysis indicates that inflammation and oxidative stress are important contributors to ALS progression in SOD1 animal models, identifies potentially critical therapeutic windows, and supports the consideration of sex-balanced and stage-specific treatment strategies at the preclinical level.},
}

Animals
*Amyotrophic Lateral Sclerosis/pathology/metabolism
*Oxidative Stress/physiology
Disease Models, Animal
*Disease Progression
*Superoxide Dismutase-1/metabolism
*Neuroinflammatory Diseases/pathology
Humans
Mice
*Inflammation/pathology
Male

@article {pmid41565302,
year = {2026},
author = {Warita, H and Urushitani, M and Atsuta, N and Izumi, Y and Kano, O and Shimizu, T and Nakayama, Y and Narita, Y and Nodera, H and Fujita, T and Mizoguchi, K and Morita, M and Aoki, M},
title = {Addendum to the 2023 clinical practice guidelines for amyotrophic lateral sclerosis in Japan: approval and integration of novel disease-modifying therapies.},
journal = {Rinsho shinkeigaku = Clinical neurology},
volume = {66},
number = {2},
pages = {67-73},
doi = {10.5692/clinicalneurol.cn-002198},
pmid = {41565302},
issn = {1882-0654},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy ; Japan ; *Practice Guidelines as Topic ; Edaravone/administration & dosage ; Vitamin B 12/administration & dosage/analogs & derivatives ; Genetic Therapy ; Drug Approval ; Oligonucleotides/administration & dosage ; Genetic Testing ; Oligonucleotides, Antisense/administration & dosage ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an intractable motor neuron disease characterized by progressive degeneration of motor neurons with varying degrees of frontotemporal lobe dysfunction. This English summary of the addendum to the Japanese clinical practice guidelines for ALS outlines major recent advances in pharmacological therapy in Japan. Following the development of the 2023 guidelines, three additional medications-oral edaravone, high-dose intramuscular mecobalamin, and tofersen-have been introduced. Oral edaravone, with its ease of administration, demonstrates pharmacokinetics comparable to the intravenous formulation. High-dose mecobalamin reduces functional decline when initiated early in the disease course. Tofersen, an antisense oligonucleotide, is the first gene-targeted therapy approved in Japan for patients with copper/zinc superoxide dismutase gene-related ALS, highlighting the importance of genetic testing and counseling in all ALS cases. This addendum provides updated expert consensus recommendations for the use, dosing, and monitoring of these therapies, while emphasizing the need for thorough communication about the ethical and psychological dimensions of genetic testing. It also addresses practical considerations for combination therapy, noting that up to three or four anti-ALS agents are now available in Japan. The long-term safety and efficacy of these therapies, as well as their potential synergistic or additive effects, remain to be clarified through real-world data and prospective registries. The objectives of this addendum are twofold: to present these advances and recommendations in English to foster international collaboration, and to inform the global ALS community about the latest therapeutic strategies in Japan. In addition, ongoing efforts to harmonize clinical evaluation standards and promote international clinical trials are highlighted, with the goal of improving patient outcomes and advancing ALS research worldwide.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy
Japan
*Practice Guidelines as Topic
Edaravone/administration & dosage
Vitamin B 12/administration & dosage/analogs & derivatives
Genetic Therapy
Drug Approval
Oligonucleotides/administration & dosage
Genetic Testing
Oligonucleotides, Antisense/administration & dosage

@article {pmid41334667,
year = {2026},
author = {Kalita, M and Jędrzejowska, M and Potulska-Chromik, A and Aragon-Gawińska, K and Franaszczyk, M and Stokłosa, T and Lipowska, M and Kostera-Pruszczyk, A},
title = {SIGMAR1 gene-related neuromuscular disorders - what do we know?.},
journal = {Neurologia i neurochirurgia polska},
volume = {60},
number = {1},
pages = {92-99},
doi = {10.5603/pjnns.106304},
pmid = {41334667},
issn = {0028-3843},
mesh = {Humans ; Sigma-1 Receptor ; *Receptors, sigma/genetics ; Child ; Male ; *Hereditary Sensory and Motor Neuropathy/genetics/diagnosis ; Mutation ; },
abstract = {INTRODUCTION: Distal hereditary motor neuropathies (dHMNs) are a clinically and genetically diverse group of rare neuromuscular disorders characterized by progressive distal muscle weakness and atrophy, often with early onset and sparing of sensory function. One subtype, Jerash-type dHMN (dHMNJ), is caused by biallelic mutations in the SIGMAR1 gene and presents with pyramidal signs in addition to distal weakness.

MATERIAL AND METHODS: A literature review was conducted by searches of the MEDLINE and PubMed databases using selected terms. Relevant original articles, case reports, case series, and reviews were selected as data sources.

DISCUSSION: SIGMAR1-related disorders (SIGMAR1-RD) encompass a broad clinical spectrum including dHMN and juvenile amyotrophic lateral sclerosis (ALS) phenotypes. The Sigma-1 receptor plays a key role in cellular stress responses, ER-mitochondria interaction, and neuronal survival. Clinical presentation often includes distal muscle weakness and atrophy with pyramidal signs.

We present a 12-year-old boy with distal muscle weakness, foot drop, and pyramidal signs. Genetic testing identified a homozygous c.247T > C (p.Phe83Leu) SIGMAR1 variant, previously classified as a variant of uncertain significance (VUS).

CONCLUSION: This article supports the pathogenicity of the c.247T > C (p.Phe83Leu) SIGMAR1 variant and underlines the need for broader genetic testing in hereditary motor neuropathies.},
}

Humans
Sigma-1 Receptor
*Receptors, sigma/genetics
Child
Male
*Hereditary Sensory and Motor Neuropathy/genetics/diagnosis
Mutation

@article {pmid41312566,
year = {2026},
author = {Kwinta, R and Morawiec, N and Bączyk, J and Kubicka-Bączyk, K and Adamczyk-Sowa, M},
title = {Aging immunity - the role of T and B cells in neurological disorders among older adults.},
journal = {Neurologia i neurochirurgia polska},
volume = {60},
number = {1},
pages = {15-25},
doi = {10.5603/pjnns.106498},
pmid = {41312566},
issn = {0028-3843},
mesh = {Humans ; *Aging/immunology ; *B-Lymphocytes/immunology ; Aged ; *T-Lymphocytes/immunology ; *Immunosenescence/immunology ; *Nervous System Diseases/immunology ; Alzheimer Disease/immunology ; Adaptive Immunity ; Parkinson Disease/immunology ; },
abstract = {INTRODUCTION: Immunosenescence is a natural process of immune system aging, which leads to significant changes in the functioning of both innate and adaptive immunity. Alterations in T and B lymphocytes can significantly impact the progression of neurological diseases including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

STATE OF THE ART: Immunosenescence affects T and B cell subsets, reducing their proliferative capacity and altering cytokine profiles. In MS, these changes promote disease progression and diminish responses to immunomodulatory therapies. In AD and PD, dysfunctional T and B cells contribute to sustained neuroinflammation, exacerbating neurodegeneration. ALS is similarly associated with altered adaptive immunity.

CLINICAL IMPLICATIONS: Recognizing how immunosenescent T and B cells contribute to disease in older adults is crucial for refining treatment strategies. These age-related immune changes may explain varied responses to therapies and highlight the need for novel approaches targeting the aged immune system in neurodegenerative diseases.

FUTURE DIRECTIONS: Future research should focus on identifying the mechanisms by which immunosenescent lymphocytes modulate neuroinflammation and neurodegeneration in aging populations. Novel biomarkers and immunomodulatory therapies tailored to older adults could significantly improve outcomes in patients with neurological diseases.},
}

Humans
*Aging/immunology
*B-Lymphocytes/immunology
Aged
*T-Lymphocytes/immunology
*Immunosenescence/immunology
*Nervous System Diseases/immunology
Alzheimer Disease/immunology
Adaptive Immunity
Parkinson Disease/immunology

@article {pmid41222474,
year = {2026},
author = {Bagheri, S and Saboury, AA and Ahmad, O and Khan, RH and Ryszkiel, I and Stanek, A},
title = {Association of mercury exposure with neurodegenerative diseases - a reality or a misconception?.},
journal = {Neurologia i neurochirurgia polska},
volume = {60},
number = {1},
pages = {26-36},
doi = {10.5603/pjnns.108158},
pmid = {41222474},
issn = {0028-3843},
mesh = {Humans ; *Neurodegenerative Diseases/chemically induced/epidemiology ; *Mercury/toxicity ; *Environmental Exposure/adverse effects ; Risk Factors ; Animals ; },
abstract = {INTRODUCTION: Exposure to heavy metals has long been considered a potential risk factor for neurodegenerative diseases.

STATE OF THE ART: Most existing studies include in vitro and animal models, and research involving human subjects has yielded conflicting results, obscuring the overall understanding of this topic.

AIMS OF THE STUDY: In this article, the aim is to clarify the situation by carefully reviewing and categorizing the available body of knowledge in this field. Specifically, the focus is on research that explores the relationship between mercury exposure and common neurodegenerative diseases.

CONCLUSIONS: Despite its neurotoxic properties, results show that mercury is not associated with frequent neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/chemically induced/epidemiology
*Mercury/toxicity
*Environmental Exposure/adverse effects
Risk Factors
Animals

@article {pmid40600544,
year = {2026},
author = {El Elhaj, A and Onger, ME},
title = {Exploring Neurodegenerative Diseases: Bridging the Gap between in vitro and in vivo Models.},
journal = {Current pharmaceutical design},
volume = {32},
number = {6},
pages = {407-414},
pmid = {40600544},
issn = {1873-4286},
mesh = {*Neurodegenerative Diseases/drug therapy/physiopathology/pathology ; Humans ; Animals ; *Disease Models, Animal ; },
abstract = {Neurological disorders are brain conditions characterized by the loss of nerve cells, leading to a decline in function. Standard examples include dementia, tremors, involuntary movements, muscle weakness, and autoimmune attacks. The most common form of dementia is Alzheimer's, affecting over 5 million elderly individuals, while tremors, stiffness, and slow movement are caused by Parkinson's. Involuntary movements and emotional problems are caused by Huntington's, while muscle weakness and eventual demise are caused by Amyotrophic lateral sclerosis. Vision problems, fatigue, and difficulty walking are caused by Multiple sclerosis (MS), an autoimmune disease that attacks the myelin sheath. In vitro models provide cost and complexity reduction, environmental control, and high-throughput. Researchers employ both cell-based (in vitro) and animal- based (in vivo) models to investigate neurodegenerative illnesses and endeavor to formulate novel treatments for diverse conditions. In vitro models provide cost and complexity reduction, environment control, and high-throughput screening of potential therapeutic agents compared to in vivo models. Nevertheless, they possess constraints, including the absence of intricate interactions that transpire in the entire organism and the inability to reproduce the disease progression completely.},
}

*Neurodegenerative Diseases/drug therapy/physiopathology/pathology
Humans
Animals
*Disease Models, Animal

@article {pmid41772347,
year = {2026},
author = {Ahuja, V and Sahu, B and Khurana, S and Kumari, K and Ganguly, NK and Gourie-Devi, M and Verma, S and Dastidar, SG and Taneja, V},
title = {Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41772347},
issn = {1559-1182},
support = {211610027970//University Grants Commission/ ; EMDR/IG/9/2024-01739//Indian Council of Medical Research/ ; 3/1/2/151/Neuro/2021-NCD-I//Indian Council of Medical Research/ ; IIRPIG-2023-0001508//Indian Council of Medical Research,India/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. Among its genetic subtypes, mutations in the fused in sarcoma (FUS) gene represent an aggressive form, often associated with early onset and rapid progression. FUS is a ubiquitously expressed DNA/RNA-binding nuclear protein involved in maintaining DNA damage repair and RNA metabolism. It also plays a crucial role in the formation of ribonucleoprotein (RNP) granules such as cytoplasmic stress granules and nuclear paraspeckles under stress. In ALS, pathogenic FUS mutations frequently disrupt the subcellular distribution of FUS, leading to cytoplasmic mislocalization and aggregation. Mutant FUS further disrupts granular dynamics by its aberrant incorporation into stress granules and altering their biophysical properties. The loss of nuclear FUS function leads to elevated levels of the long non-coding RNA NEAT1 and enhanced paraspeckle assembly with disrupted structural integrity. The impaired nucleocytoplasmic granular dynamics compromise the cellular resilience, thereby increasing motor neuron vulnerability. The interaction of FUS with other ALS-associated proteins causes pathological alterations in the cellular milieu, suggesting a common underlying disease mechanism. This comprehensive review emphasizes the FUS-mediated RNP granule regulation under physiological and pathological conditions. Further, clinically approved and emerging therapeutic strategies aimed at attenuating FUS pathology and RNP granule dynamics have been described.},
}

@article {pmid41768173,
year = {2026},
author = {Capitani, G and Lozzi, D and Curcio, G and Migliore, S},
title = {Moral decision-making in patients with neurodegenerative diseases: a systematic review.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1745923},
pmid = {41768173},
issn = {1664-1078},
abstract = {INTRODUCTION: Moral decision-making, a core component of social cognition, relies on integrating affective and cognitive processes supported by distributed neural networks. Neurodegenerative diseases disrupt these systems to varying degrees, offering unique models to investigate the neural bases of moral cognition. This review aimed to systematically examine moral decision-making deficits across neurodegenerative diseases, delineate disease-specific patterns of moral cognition impairment, and highlight conceptual and methodological gaps to inform future research and clinical assessment.

METHODS: A systematic search of PubMed, Web of Science, and Scopus was conducted for studies published up to January 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

RESULTS: Seventeen studies met inclusion criteria. Convergent evidence indicates that behavioral variant frontotemporal dementia (bvFTD) produces a distinctive utilitarian bias characterized by diminished empathy, emotional blunting, and impaired integration of intention and outcome, reflecting degeneration of the ventromedial prefrontal cortex, anterior insula, and amygdala within the salience and default mode networks. In contrast, Alzheimer's disease (AD) patients typically preserve affective aversion to harm, suggesting relative sparing of limbic-ventromedial circuits despite conceptual and executive decline. Moral reasoning in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) remains largely intact unless frontotemporal involvement occurs, while dementia with Lewy bodies (DLB) manifests intermediate profiles marked by reduced cognitive theory of mind and aberrant moral affect.

DISCUSSION: These findings delineate disease-specific patterns of moral dysfunction linked to network-level degeneration rather than global cognitive decline. Understanding these mechanisms holds translational relevance for early diagnosis, ethical capacity assessment, and the development of ecologically valid tools to monitor socio-emotional deterioration in neurodegenerative disorders.},
}

@article {pmid41767843,
year = {2026},
author = {Ben Khalaf, N},
title = {Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1711422},
pmid = {41767843},
issn = {1663-4365},
abstract = {The maintenance of protein homeostasis is essential for neuronal survival and function; however, it progressively declines with age, predisposing the brain to neurodegenerative diseases. Molecular chaperones Hsp70 and Hsp90 are key guardians of proteostasis, pivotally regulating protein folding, refolding, and degradation under both physiological and stress conditions. This review integrates an overview of the structural features, isoforms, and mechanistic interactions of Hsp70 and Hsp90. It highlights how their dysfunction contributes to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. We first examine the architecture and ATP-driven chaperone cycles of Hsp70 and Hsp90, their co-chaperone networks, and the feedback regulation by the Heat Shock Factor-1 pathway. We then discuss evidence linking age-related declines in chaperone expression and HSF-1 activity to proteostasis collapse and neuronal vulnerability. The review particularly examines how Hsp70 and Hsp90 differentially influence pathogenic protein aggregation (e.g., tau, α-synuclein, TDP-43, and mutant huntingtin) and how this balance is altered in the aging brain. Regarding therapeutic approaches, we summarize current strategies targeting these chaperones, including small-molecule modulators of Hsp70 and Hsp90, co-chaperone inhibitors, and recombinant chaperone therapy, which has shown to restore proteostasis and cognitive function in experimental models. These emerging interventions underscore the dual nature of Hsp70/Hsp90 systems, acting as both protectors and potential contributors to neurodegeneration, depending on their regulation and interaction context. By linking molecular chaperone biology to aging and translational therapeutics, this review establishes a framework for developing precision approaches that enhance proteostasis capacity, delay age-associated neurodegeneration, and promote healthy brain aging.},
}

@article {pmid41765206,
year = {2026},
author = {Kotapati, C and Van Tran, LT and Cardoso, FC},
title = {Voltage-gating and neuronal signalling in neurodegeneration: From neuropathology to therapeutic opportunities in motor neuron disease.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107336},
doi = {10.1016/j.nbd.2026.107336},
pmid = {41765206},
issn = {1095-953X},
abstract = {Voltage-gated ion channels (VGICs) are central to motor neuron excitability, governing the initiation and propagation of action potentials and synaptic transmission. Disruption of their finely tuned gating properties contributes to pathology-associated hyperexcitability, a hallmark of several neurodegenerative conditions, including motor neuron disease (MND). In this review, we examine the physiological roles of voltage-gated sodium, calcium and potassium channels in motor neurons, and evaluate how mutations, altered expression, aberrant biophysics, and maladaptive signalling impair the voltage signalling processes that drive and underlie neuronal dysfunction and degeneration. We synthesise evidence linking ion channel dysfunction to altered excitability, excitotoxicity, impaired neurotransmission, motor system instability and progressive motor neuron loss in MND. We discuss current therapies that offer modest benefit and may act directly or indirectly on neuronal excitability but with limited target specificity. Motivated by the the urgent need for effective treatments for MND, we discuss emerging strategies that leverage highly selective VGIC modulators, particularly gating-modifier peptides inhibitors, to counteract hyperexcitability in MND. We further highlight that understanding how voltage-sensing and channel gating are altered in MND offers new avenues for selective targeted intervention. Together, the evidence supports VGICs as critical yet poorly explored therapeutic targets for halting motor neurodegeneration.},
}

@article {pmid41763443,
year = {2026},
author = {Zafarjonovna, AZ and Aysulu, E and Matlyuba, S and Rashid, H and Azamatovich, JB and Ahmadjon, A and Barno, A and Kurbanovna, AM and Ugli, MRM and Shaxodat, I and Rustam, T and Jumaniyazovna, MG and Ishankulov, A},
title = {Small extracellular vesicles as emerging biomarkers and therapeutic targets in neurodegenerative diseases.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {120932},
doi = {10.1016/j.cca.2026.120932},
pmid = {41763443},
issn = {1873-3492},
abstract = {Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood-brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.},
}

@article {pmid41762823,
year = {2026},
author = {Nissinen, P and Silén-Lipponen, M and Kähkönen, O and Saaranen, T},
title = {Nursing students' learning experiences, outcomes, and methods in distance education: An integrative literature review.},
journal = {Nurse education today},
volume = {162},
number = {},
pages = {107051},
doi = {10.1016/j.nedt.2026.107051},
pmid = {41762823},
issn = {1532-2793},
abstract = {BACKGROUND: The transformation of nursing education has emphasized the role of distance education as a permanent component. Nursing students' learning experiences and outcomes in this format show considerable variation and raise questions about the most effective distance learning methods.

AIMS: The aim of this integrative review was to explore nursing students' experiences with distance learning, identify the learning outcomes it produces, and examine the distance learning methods used in nursing education.

DESIGN: Integrative literature review.

METHODS: A systematic literature search was conducted in the CINAHL (EBSCO, PubMed/Medline, Education database (ProQuest), Scopus and ERIC (EBSCO) databases, including peer-reviewed studies published in English between 2018 and 2024. The review followed the PRISMA 2020 guidelines. Quality appraisal was performed using Hawker et al.'s evaluation tool. Data was analyzed using inductive content analysis.

RESULTS: A total of 43 studies were included in the review. Five main themes were identified describing students' experiences: the accessibility of digital learning platforms, the quality and structure of learning materials, the acquisition of practical and clinical skills, social interaction and peer support, motivation, self-regulation, and emotional well-being. Learning outcomes were categorized into cognitive, psychomotor, and affective domains. The most common learning methods included synchronous, asynchronous, and blended approaches, with blended learning showing particularly positive results.

CONCLUSION: Distance education can support nursing students' learning when it is well-structured and combines pedagogical planning with interactive and practical elements. Not all competencies, particularly clinical skills, can be taught remotely. The learning experience is shaped by individual abilities, guidance, and technical conditions, and distance education may not suit all students equally well. Effective methods, especially blended learning, support engagement and learning when aligned with student needs and pedagogical goals.},
}

@article {pmid41746390,
year = {2026},
author = {Kural, I and M Mombeek, LM and Wilson, DM},
title = {Role of mitochondria in neuronal function and survival in the enteric and central nervous systems.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {83},
number = {1},
pages = {},
pmid = {41746390},
issn = {1420-9071},
support = {11P4G24N//Fonds Wetenschappelijk Onderzoek/ ; G0A9625FWO//Fonds Wetenschappelijk Onderzoek/ ; },
abstract = {UNLABELLED: Mitochondria are indispensable organelles that not only generate cellular energy through oxidative phosphorylation but also regulate calcium homeostasis, redox balance, and apoptotic signaling. Given the high metabolic demands of neurons, mitochondrial function and resilience mechanisms are essential for neuronal development, maturation, and survival; when these systems fail, pathological outcomes can arise. This review highlights the critical role of mitochondria in maintaining neuronal function, with discussion related to both the central (CNS) and enteric (ENS) nervous systems. We present how mitochondrial dysfunction, through impaired bioenergetics, oxidative stress, defective quality control, and altered dynamics, can drive neuronal cell loss. Furthermore, we highlight the link between mitochondrial defects and nervous system pathological outcomes in both primary mitochondrial disorders, such as mitochondrial neurogastrointestinal encephalomyopathy, and secondary mitochondrial disorders, such as Alzheimer, Parkinson, and Huntington disease, as well as amyotrophic lateral sclerosis. By integrating evidence from the CNS and ENS, this review highlights the central role of mitochondria in supporting and preserving neuronal health, as well as the potential of mitochondria as therapeutic targets in neurodegenerative disease.

GRAPHICAL ABSTRACT: [Image: see text]},
}

@article {pmid41762049,
year = {2026},
author = {Zhang, Y and Chen, B and Lin, Y and Kang, D and Zhao, T},
title = {Advances and Challenges in the Use of Spinal Cord Organoids in ALS.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {2},
pages = {44709},
doi = {10.31083/JIN44709},
pmid = {41762049},
issn = {0219-6352},
support = {82301543//National Natural Science Foundation of China/ ; 2021QNA025//Youth Scientific Research Project of Fujian Provincial Health Commission/ ; 2021Y2001//Technology Platform Construction Project of Fujian Province/ ; 2020Y2003//Technology Platform Construction Project of Fujian Province/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease. No effective treatments have yet been found for ALS, primarily because the molecular mechanisms that underlie its pathogenesis are unknown. Although animal models are suitable for ALS research, species differences between these models and human spinal cord organs make it difficult to accurately predict the progression of disease in humans. Therefore, the development of more suitable models is urgently needed. Human stem cells have unlimited development potential and can be used to make three-dimensional organoid structures that mimic the architecture and function of actual organs. Organoid models can be used to overcome some of the species differences and accelerate experimental research, leading to the development of practical applications for the treatment of ALS. This article discusses the pathological mechanisms and cell types involved in ALS, as well as the genes associated with this disease. We also discuss the possible applications of spinal cord organoids (SCOs) in ALS research, such as the modeling of disease characteristics, study of pathological mechanisms, and drug screening. Finally, the prospects for SCOs in ALS treatment are highlighted, while acknowledging the need for further development of relevant technologies.},
}

@article {pmid41759446,
year = {2026},
author = {Salmon, PM and King, B and Hall, D and McLean, S and Thompson, J and Cooke, N and Salas, E and Loft, S and Read, GJM},
title = {The big five model of teamwork and human autonomy teams: a scoping review.},
journal = {Applied ergonomics},
volume = {135},
number = {},
pages = {104761},
doi = {10.1016/j.apergo.2026.104761},
pmid = {41759446},
issn = {1872-9126},
abstract = {Teams play a critical role in society and represent a key area for Human Factors and Ergonomics. Salas et al.'s Big Five model is widely cited; however, the increasing use of Human-Autonomy Teams (HATs) has fuelled debate over its continued relevance. It is important to reflect on how the Big five model has been applied, in what contexts, and whether applications to contemporary teams are emerging. This article presents the findings from a scoping review undertaken to identify and synthesise the peer reviewed literature describing applications of the Big Five model. Articles were deemed eligible for inclusion if they were published in the peer reviewed literature and described an application of the Big Five model to study teamwork. 38 articles were included in the review and no applications of the Big Five model to study HATs were identified. Over half of the studies were undertaken in healthcare and a range of assessment methods have been used (e.g., questionnaires, surveys, interviews, observer-rating scales, communication transcript analysis). Just under a third of included studies evaluated all model components (i.e., the five processes and three coordinating mechanisms) and few considered the relationships between model components or between model components and team effectiveness. Research is required to explore the validity of the Big Five model for HATs, to gather evidence for the relationship between model components and team effectiveness, and to develop more precise Big five-based measures.},
}

@article {pmid41752118,
year = {2026},
author = {Kurdi, MA and Alotaibi, H and Alkhuraymi, AT and Aldahery, LN and Alhawaj, AF and Aldali, HJ},
title = {Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41752118},
issn = {1422-0067},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut-brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.},
}

@article {pmid41751793,
year = {2026},
author = {Ptáček, O and Musil, Z and Guarnieri, G and Vrbacká, A and Moudrá, P and Zlámalová, A and Röszlerová, P and Tonhajzer, M and Musil, V and Morelli, A and Zach, P},
title = {Amyotrophic Lateral Sclerosis: The State of the Art on Treatments and the Therapeutic Role of the Intestinal Microbiome in Human Studies.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41751793},
issn = {1422-0067},
support = {Cooperatio 39 - Oncology and Haematology//Charles University/ ; Cooperatio 33-Intensive Care Medicine//Charles University/ ; Cooperatio 36-Medical Diagnostics and Basic Medical Sciences//Charles University/ ; #NEXTGENERATIONEU//European Commission/ ; MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DR. 1553 11.10.2022)//Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder; to date, there is no long-term effective treatment. Recently, a relationship has been discovered between the human intestinal microbiome and the pathogenesis of ALS, on which basis faecal microbiota transplantation (FMT) has been proposed as a potential treatment for ALS. In this review, we compare three existing case studies examining the effect of FMT on the course of ALS, highlighting differences in methodology and results. In two of the studies, a halt in the progression of ALS symptoms was observed following FMT, accompanied by improvement in patient health. However, in the third and largest study, no significant effect of FMT was observed. The possible explanation for this discrepancy may be the intentional depletion of intestinal microorganisms using antibiotics prior to FMT in the third study. Future studies and/or completion of the ongoing clinical studies will help clarify the therapeutic effectiveness of FMT in ALS patients.},
}

@article {pmid41751374,
year = {2026},
author = {Trabulo, A and Sousa, P and Alvites, R and Maurício, AC},
title = {Mesenchymal Stem Cell-Based Therapies Applied in Neurological Diseases: A Systematic Review.},
journal = {Biomedicines},
volume = {14},
number = {2},
pages = {},
pmid = {41751374},
issn = {2227-9059},
abstract = {Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients' quality of life, and effective treatments remain limited. As the focus is on treating the symptoms, the root cause of the problem is commonly not addressed. Mesenchymal stem cells show an emerging potential due to the ability for self-renewal combined with their capability for differentiation into various cell lines, which makes them a strong candidate for regenerative therapies in general, and for application in neurological issues in particular. This article provides an overview of the safety, efficacy, and challenges associated with the use of mesenchymal stem cells (MSCs) and their derived secretome in clinical and preclinical models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Methods: A systematic search was conducted on PubMed to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSCs' paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Integration of genetic engineering, preconditioning, and EV technology may represent an emerging therapeutic approach that may complement existing neuroregeneration treatments, offering a scalable and minimally invasive frontier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.},
}

@article {pmid41750236,
year = {2026},
author = {Eisen, A},
title = {Exploring the ALS Multistep Model.},
journal = {Brain sciences},
volume = {16},
number = {2},
pages = {},
pmid = {41750236},
issn = {2076-3425},
abstract = {ALS is a multistep disease, in which (epi)genetic, environmental, and age-related processes, including senescence, converge over decades to reduce resilience resulting in self-sustaining symptomatic disease. The multistep model visualizes five to six impactful events in sporadic ALS, but fewer in those carrying high-penetrance mutations, such as SOD1, FUS, or C9orf72 expansions. The timing, duration, and cumulative effects of specific steps are presumed to have individual variability but, the steps themselves are inferred since they have not been observed and remain agnostic as to biological identity. Nevertheless, the model gives an opportunity to integrate genetics, aging, environmental exposures, and systems-level vulnerability into a single framework. Acting as step modifiers, environmental exposures including trauma lower the threshold for step acquisition, accelerate the accumulation of steps, influence the anatomical site of disease onset, and unmask preclinical disease. Because ALS emerges from the gradual collapse of multiple layers of biological robustness, tackling a single pathway will be insufficient and the multistep model forces a reconsideration of therapeutic timing and strategies. Protection against early-life insults, anti-aging, and anti-senescent therapies may curtail step accumulation preventing ALS from exceeding threshold and disease manifestation.},
}

@article {pmid41746412,
year = {2026},
author = {Tarazona-Santabalbina, FJ and Belenguer-Varea, A and Borrás-Blasco, J and García-Tercero, E and Martin, ML and Prior, NP and Mariscal, G and Valcuende-Rosique, A},
title = {Safety profile of tofersen in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {},
pmid = {41746412},
issn = {1590-3478},
}

@article {pmid41745965,
year = {2026},
author = {Haroun, M and Tratrat, C and Mathew, RT and Munir, M and Sattar, MN and Shawky, M and Kochkar, H and Aldakhilallah, ON and Ghafoor, A and Turk, KGB and Geronikaki, A and Ghazzawy, HS},
title = {Avian Candidiasis: A Comprehensive Review of Pathogenesis, Diagnosis, and Control.},
journal = {Veterinary sciences},
volume = {13},
number = {2},
pages = {},
pmid = {41745965},
issn = {2306-7381},
support = {Grant number: KFU260519//Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia/ ; },
abstract = {This review is a comprehensive investigation of avian candidiasis, mainly caused by Candida albicans, although the prevalence of non-albicans Candida species has increased in domestic and wild birds. Avian candidiasis causes significant economic losses in poultry production through increased mortality, cost of treatments, and reduced growth rates, particularly in young birds and intensive farming operations. The pathogenesis section provides a description of the molecular virulence factors such as adhesin-mediated attachment (ALS, Agglutinin-Like Sequence family; HWP1, Hyphal Wall Protein 1), yeast-to-hypha morphogenesis, tissue damage by Candidalysin, biofilm formation on mucosal and abiotic surfaces, and secreted hydrolytic enzymes including secreted aspartyl proteinases (SAPs) and phospholipases. The identified predisposing factors include immunosuppression, malnutrition, abuse of antibiotics, bad husbandry, and crop stasis. The diagnostic methods discussed encompass cytological analysis and fungal culture on selective media to more sophisticated methods of molecular analysis (PCR, MALDI-TOF MS, and NGS). Antifungal susceptibility investigations indicate that nystatin and amphotericin B are still very effective against most avian isolates and that resistance to the azoles is on the rise, especially with respect to the non-albicans Candida species. Nystatin is still the first-line treatment of localized infections; azoles are still used for resistant or systemic infections despite their hepatotoxicity. Sanitation, proper nutrition, and proper use of antimicrobials are essential to prevent diseases. The knowledge gaps comprise the absence of avian-specific pharmacokinetic information, poor knowledge of species-species virulence phenotypes, and the lack of point-of-care diagnostics. The need to have integrated One Health surveillance systems is emphasized by the zoonotic potential of the avian Candida reservoirs.},
}

@article {pmid41744765,
year = {2026},
author = {Dellazizzo Toth, T and Bond, S and Saxena, S},
title = {The Calcium Connection: Explaining Motor Neuron Vulnerability in ALS.},
journal = {Cells},
volume = {15},
number = {4},
pages = {},
pmid = {41744765},
issn = {2073-4409},
abstract = {ALS is a severe neuromuscular disease classically characterized by the progressive loss of motor neurons, leading to incremental muscle weakness and eventually death. Current treatment options for ALS have proven to have limited effect, merely delaying the progression of symptoms and prolonging patient survival. This motor neuron subtype-related differential vulnerability has been linked to neuron excitability, metabolism, and protein aggregation. Calcium dysregulation, which serves as an important second messenger in neural signaling pathways, has been implicated in each of these mechanisms and represents a potential target for therapeutic intervention. Armed with cutting-edge tools for visualizing and recording calcium transients in vivo, ALS researchers have delved deeper into the role of calcium dysregulation in disease in recent years. Vulnerable motor neuron populations display an excess of calcium-permeable ion channels together with reduced expression of calcium-binding proteins, generating a cellular environment primed for excitotoxic stress. Loss of inhibitory synaptic input further heightens susceptibility to calcium overload. Paradoxically, some evidence suggests that elevated neuronal activity can exert neuroprotective effects, highlighting the complexity of activity-dependent calcium signaling in ALS. Additionally, ALS-related toxic protein accumulation disrupts calcium homeostasis, contributing to endoplasmic reticulum stress and mitochondrial dysfunction. Emerging data indicate that calcium dysregulation impairs neuron-glia communication, amplifying neuroinflammation and accelerating disease progression. This review aims to synthesize current evidence on how calcium imbalance contributes to motor neuron vulnerability and degeneration in ALS. By exploring the cellular, synaptic, and network-level mechanisms of calcium dysregulation in ALS, the review examines its interplay with mitochondrial and ER stress and explores its impact on neuron-glia interactions with the aim of synthesizing key mechanistic insights into the disease pathogenesis and therapeutic targets.},
}

@article {pmid41743427,
year = {2026},
author = {Luo, Y and Liu, X and Yang, M},
title = {Current status and future prospects of brain-computer interfaces in the field of neurological disease rehabilitation.},
journal = {Frontiers in rehabilitation sciences},
volume = {7},
number = {},
pages = {1666530},
pmid = {41743427},
issn = {2673-6861},
abstract = {Neurological disorders represent a significant category of diseases that profoundly affect human health, accounting for the second leading cause of global mortality. This group of conditions includes stroke, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury, Parkinson's disease, and cerebral palsy, among others. These disorders are highly susceptible to sequelae and profoundly impact individuals' daily lives. In this context, Brain-Computer Interface (BCI) technology has demonstrated considerable potential in the domain of neurorehabilitation, although numerous challenges remain. The manuscript provides a comprehensive review of recent advancements in research and clinical applications, highlighting current limitations and outlining future directions. It elucidates the applicability and constraints of Brain-Computer Interface (BCI) technology across various diseases and patient populations. To facilitate insights across different conditions, comparative tables are presented, aligning BCI strategies with therapeutic targets, outcomes, advantages, limitations, and existing evidence gaps. The scope extends beyond motor restoration to include under-explored domains, such as neuropathic pain, with a focus on real-world translation, including home and community feasibility and the distinction between assistive and rehabilitative applications. The review distills overarching limitations within the field, such as small sample sizes, protocol heterogeneity, and limited longitudinal evidence, while synthesizing the most recent studies. An actionable research and development roadmap is proposed to guide next-generation BCI rehabilitation, incorporating individualized cortical-network simulators, self-architecting decoders, adaptive therapy approaches akin to game seasons, and proprioceptive "write-back" mechanisms via peripheral interfaces. Moreover, the review reveals significant research focal points and critical issues that warrant further investigation in the context of neurological rehabilitation utilizing BCI technology.},
}

@article {pmid41741312,
year = {2026},
author = {Herrero Babiloni, A and Dal Fabbro, C and Samin, F and Schmittbuhl, M and Blanchet, PJ and Lavigne, GJ and Rouleau, G},
title = {The role of dentists in the recognition of neurodegenerative and systemic conditions with neurological involvement.},
journal = {Oral surgery, oral medicine, oral pathology and oral radiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oooo.2026.01.010},
pmid = {41741312},
issn = {2212-4411},
abstract = {Dentists are often the first healthcare providers to observe subtle orofacial and behavioral changes that may reflect underlying neurological diseases, including altered salivary flow, dysphagia, oral burning sensations, unusual orofacial movements, or tremors and pain, among others. These are symptoms of conditions such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and other systemic disorders with neurological involvement, which are frequently misattributed to local or functional causes, thereby delaying diagnosis and care. As the frequency of neurodegenerative and neuromuscular conditions rises with aging, the dental setting offers a critical opportunity for early recognition and referral. This clinical review summarizes orofacial manifestations, dental care challenges, and referral strategies across different neurological and systemic diseases. Organized by disease stage and functional impairment, the review provides practical tools for decision-making. Guidance on screening, behavioral adaptation, and care coordination is also provided, including multiple practical tables, figures, and chairside screening tools to support early recognition and referral. Finally, the review advocates for improved training, interdisciplinary collaboration, and progressive integration of artificial intelligence, machine learning, and other emerging technologies (e.g., biosensors, salivary biomarker platforms, or high-density electrophysiologic tools) to support clinicians in recognizing neurological diseases.},
}

@article {pmid41737317,
year = {2026},
author = {Luo, R},
title = {Next questions of autophagy in neurodegenerative diseases: From mechanisms to therapeutics.},
journal = {Innovation (Cambridge (Mass.))},
volume = {7},
number = {1},
pages = {100989},
pmid = {41737317},
issn = {2666-6758},
abstract = {Autophagy, a key cellular degradation pathway, is central to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Despite progress in understanding its role, critical questions remain. This perspective highlights pressing issues, including cell-type-specific autophagy regulation, interactions with other cellular pathways, and challenges in translating autophagy-modulating therapies to clinical practice. Addressing these questions will advance our understanding of neurodegenerative diseases and pave the way for novel therapeutics.},
}

@article {pmid41734662,
year = {2026},
author = {Alam, P and Hasan, GM and Mohammad, T and Hassan, MI},
title = {Next-generation computational strategies for neurodegenerative biomarkers: Multi-omics integration, AI, and molecular modeling.},
journal = {Computational biology and chemistry},
volume = {123},
number = {},
pages = {108973},
doi = {10.1016/j.compbiolchem.2026.108973},
pmid = {41734662},
issn = {1476-928X},
abstract = {Neurodegenerative diseases (NDs) are progressively debilitating conditions driven by complex molecular perturbations and selective neuronal loss. Conventional approaches to discovering biomarkers, using single-omics or empirical screening, often fail to capture the multi-factorial nature of these disorders. It is now possible to integrate large-scale omics data with structural and molecular modeling methods to reveal mechanistically relevant biomarkers using integrative computational biology. Here, we review recent advances in integrative computational strategies that combine multi-omics, encompassing genomics, transcriptomics, proteomics, and metabolomics, with structural bioinformatics and molecular modeling to identify mechanistically informative biomarkers. We cover systems-level and network-based integration methods, machine learning (ML) and artificial intelligence (AI) frameworks, and structure-guided validation approaches, including homology/AI-based modeling, molecular docking, and molecular dynamics. We also discuss case studies illustrating how omics-based predictions are validated through protein structure modeling to identify key biomarkers and therapeutic targets. Finally, we discuss major challenges, such as data heterogeneity, reproducibility, and limitations of structural modeling, and emerging trends, such as AI-powered multi-omics, single-cell spatial profiling, and digital twin simulations. Together, the integrative computational strategies are likely to accelerate the discovery of reliable, mechanistically informative, and clinically translatable biomarkers for precision medicine in NDs.},
}

@article {pmid41731547,
year = {2026},
author = {Jammal, JK and Gomez, EA and Al-Chalabi, A and Iacoangeli, A},
title = {Classification of ALS molecular subtypes: a literature review on machine learning applications and their clinical value.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04725-y},
pmid = {41731547},
issn = {1741-7015},
support = {772376-EScORIAL/ERC_/European Research Council/International ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by considerable heterogeneity in both its underlying biological mechanisms and clinical presentation. High-dimensional transcriptomic datasets offer an opportunity to characterise this variation at the molecular level; however, traditional statistical methods struggle with their scale and complexity.

MAIN BODY: Machine learning approaches can reduce dimensionality and uncover latent patterns, enabling the identification of molecular subtypes that may refine prognosis and support patient stratification. Recent transcriptomic studies employing unsupervised machine learning have identified ALS subtypes with distinct molecular and clinical characteristics. Redefining ALS into more homogeneous molecular and clinical subtypes could transform all areas of ALS research by supporting novel experimental designs and precision medicine approaches.

CONCLUSIONS: In this review, we summarise and critically assess these studies, discussing their findings, strengths, and limitations, and highlighting research gaps and challenges that must be addressed to enable their translation into biomedical and clinical practice.},
}

@article {pmid41729684,
year = {2026},
author = {Paulo-Ramos, A and Rhymes, ER and Villarroel-Campos, D and Sleigh, JN},
title = {Disruption of BDNF signalling in neuropathologies.},
journal = {Biochemical Society transactions},
volume = {54},
number = {2},
pages = {},
doi = {10.1042/BST20253079},
pmid = {41729684},
issn = {1470-8752},
support = {MR/Y010949/1/MRC_/Medical Research Council/United Kingdom ; 23GRO-PG36-0675-1//Muscular Dystrophy UK/ ; },
mesh = {*Brain-Derived Neurotrophic Factor/metabolism/genetics ; Humans ; *Signal Transduction ; Animals ; Receptor, trkB/metabolism ; Neuronal Plasticity ; Neurons/metabolism ; },
abstract = {The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities of this neurotrophin, which is reliant upon TrkB and p75NTR receptors, have been well characterised in both health and disease. This review summarises the latest findings on BDNF dysregulation in neuropathologies. Indeed, across diseases of both the central and peripheral nervous systems, BDNF signalling is frequently disrupted, contributing to neuronal dysfunction and degeneration. Consequently, through direct or indirect enhancement of its expression and/or function, BDNF has proved to be a promising therapeutic target across many neurological conditions. However, the complexity of its regulation and interaction with several different receptors underpins the need for further research to deepen our understanding of BDNF disruption in neuropathologies and to achieve its therapeutic potential.},
}

*Brain-Derived Neurotrophic Factor/metabolism/genetics
Humans
*Signal Transduction
Animals
Receptor, trkB/metabolism
Neuronal Plasticity
Neurons/metabolism

@article {pmid41724277,
year = {2026},
author = {Zhao, X and Pu, L and Zeng, X and Nie, J},
title = {Role of nuclear import proteins in maintaining proteostasis and disease pathogenesis.},
journal = {Biochemical pharmacology},
volume = {248},
number = {},
pages = {117831},
doi = {10.1016/j.bcp.2026.117831},
pmid = {41724277},
issn = {1873-2968},
abstract = {Nuclear import receptors (NIRs), particularly the importin α/β heterodimer system, function as essential gatekeepers of nucleocytoplasmic trafficking by decoding diverse nuclear localization signals (NLSs) to orchestrate cellular proteostasis. This review delineates the structural basis of NLS recognition and the coordinated mechanisms that facilitate the nuclear import of critical cargoes, including transcription factors, RNA-binding proteins, and DNA repair factors. Beyond their canonical transport role, we emphasize the emerging functions of NIRs as molecular chaperones that suppress aberrant phase separation and their co-translational regulatory roles in ensuring proper protein biogenesis and folding. The collapse of these regulatory functions underpins the pathogenesis of major human diseases. We examine in detail the pathological consequences of nuclear import dysfunction, highlighting its central role in specific neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), oncogenic transformation, and viral pathogenesis. The discussion provides a critical appraisal of emerging therapeutic strategies that target the nuclear import machinery, including small-molecule inhibitors (e.g., importazole, ivermectin), peptide competitors, and advanced delivery platforms. We conclude by providing the associated challenges such as achieving tissue specificity, avoiding off-target effects and the significant opportunities that lie in pharmacologically modulating this fundamental pathway to restore proteostasis and develop disease modifying therapies.},
}

@article {pmid41720758,
year = {2026},
author = {Falahati, M and Orangi, K and Shaabanpoor Haghighi, A and Pouroushaninia, N and Niknam, N and Soltani, S and Radnia, P and Arab Bafrani, M and Shirdel, S and Aarabi, MH},
title = {Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {41720758},
issn = {2191-0200},
abstract = {Diffusion tensor imaging (DTI) is a valuable method for evaluating microstructural changes in the amygdala associated with neurodegenerative and neuroinflammatory disorders. This systematic review examines amygdala microstructural alterations in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), and multiple sclerosis (MS) using DTI metrics. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Web of Science databases through August 2025, identifying 4,442 records. After screening and eligibility assessment, 13 studies were included, comprising 1,412 patients and 1,146 healthy controls. Due to sample heterogeneity and lack of standardized effect size measures, meta-analysis was not performed. Across disorders, elevated mean diffusivity (MD) emerged as the most consistent finding, present in 100 % of AD patients and observed in all examined conditions. Reduced fractional anisotropy (FA) was the second most frequent alteration, with 36.6 % of AD patients showing decreased FA. In MS, increased radial diffusivity (RD) was prominent, while longitudinal DLB studies revealed progressive free water (FW) increases. These DTI-based microstructural changes often preceded volumetric atrophy and correlated with clinical severity. Our findings demonstrate that DTI metrics, particularly MD and FA, serve as sensitive markers of amygdala pathology across neurodegenerative diseases and may facilitate early diagnosis, disease monitoring, and differential diagnosis of these conditions.},
}

@article {pmid41718986,
year = {2026},
author = {Shadfar, S and Assar Kashani, S and Gautam, S and Takalloo, Z and Farzana, F and Parakh, S and Atkin, JD},
title = {The Role of the Golgi Apparatus in Neurodegeneration.},
journal = {Sub-cellular biochemistry},
volume = {111},
number = {},
pages = {413-440},
pmid = {41718986},
issn = {0306-0225},
mesh = {*Golgi Apparatus/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Neurons/metabolism/pathology ; },
abstract = {The Golgi apparatus has important, well characterised functions in the trafficking, processing, and post-translational modification of proteins and lipids. However, roles in other cellular processes are increasingly reported, including autophagy, apoptosis, DNA repair, and cytoskeletal (microtubules and actin) function. The Golgi therefore serves as a regulatory hub for multiple signalling pathways that maintain essential cellular activities. The Golgi normally consists of flattened stacks of membrane (cisternae), but during normal physiology and pathological conditions it 'fragments', resulting in altered morphology and distribution. This is well described as an early pathological feature of many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) and prion diseases, and amyotrophic lateral sclerosis (ALS). These age-related conditions are characterised by the death of neurons: highly specialised, unique cells that form the foundation of the nervous system. Interestingly, many Golgi-related functions are also dysregulated in these diseases. However, this has received relatively little attention compared to other pathogenic mechanisms. The Golgi apparatus in neurons shares features common to other eukaryotic cells but it also has unique properties, such as the presence of distinctive assemblies: Golgi outposts and satellites, which remain poorly characterised. Here we discuss the increasing evidence describing dysfunction and fragmentation of the Golgi apparatus and its possible role in the pathogenesis of neurodegenerative diseases.},
}

*Golgi Apparatus/metabolism/pathology
Humans
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Neurons/metabolism/pathology