Rising Voltage-Gated Potassium Channel Antibody Level as a Possible Disease Progression Marker for Amyotrophic Lateral Sclerosis: A Case Report

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A subset of amyotrophic lateral sclerosis (ALS) patients tests positive for antibodies commonly associated with autoimmune neurological diseases, including voltage-gated potassium channel (VGKC)-complex antibodies. Although an basis ALS remains speculative, and immunomodulatory therapies have shown minimal benefit as yet, isolated cases suggest that VGKC-complex may be relevant to disease type progression. In this report, we present a case in which increasing antibody levels correlated clinical decline, raising the question whether such could serve biomarkers progression antibody-positive patients. To date, no published studies systematically evaluated changes over time. Our findings tracking offer insights into prompt further investigation their potential role prognostic biomarkers, especially certain subtypes disease.

Language: Английский

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New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the ‘dying back’ hypothesis

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(11)

Published: Nov. 1, 2024

Abstract Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, characterized by muscle weakness, paralysis ultimately, respiratory failure. The exact causes of ALS are not understood, though it believed to combine genetic environmental factors. Until now, was admitted motor neurons (MN) cord degenerate, leading weakness paralysis. However, as symptoms typically begin with or stiffness, new hypothesis has recently emerged explain development pathology, is, ‘dying back hypothesis’, suggesting this degeneration starts at connections between MN muscles, resulting loss function. Over time, damage extends along length MN, ultimately affecting their cell bodies brain. While dying provides potential framework for understanding progression ALS, mechanisms underlying remain complex fully understood. In review, we positioning role extracellular vesicles actors development.

Language: Английский

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Studies of Genetic and Proteomic Risk Factors of Amyotrophic Lateral Sclerosis Inspire Biomarker Development and Gene Therapy

Cells, Journal Year: 2023, Volume and Issue: 12(15), P. 1948 - 1948

Published: July 27, 2023

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease affecting the upper and lower motor neurons, leading to muscle weakness, impairments, disabilities death. Approximately 5–10% of ALS cases are associated with positive family history (familial or fALS), whilst remainder sporadic (sporadic ALS, sALS). At least 50 genes have been identified as causative risk factors for ALS. Established pathogenic variants include superoxide dismutase type 1 (SOD1), chromosome 9 open reading frame 72 (c9orf72), TAR DNA Binding Protein (TARDBP), Fused In Sarcoma (FUS); additional ALS-related including Charged Multivesicular Body 2B (CHMP2B), Senataxin (SETX), Sequestosome (SQSTM1), TANK Kinase (TBK1) NIMA Related (NEK1), identified. Mutations in these could impair different mechanisms, vesicle transport, autophagy, cytoskeletal mitochondrial functions. So far, there no effective therapy against Thus, early diagnosis predictions remain one best options symptomologies. Proteomic biomarkers, microRNAs, extracellular vehicles (EVs) serve promising tools progression assessment. These markers relatively easy obtain from blood cerebrospinal fluids can be used identify potential genetic even preclinical stage before symptoms appear. addition, antisense oligonucleotides RNA gene therapies successfully employed other diseases, such childhood-onset spinal muscular atrophy (SMA), which also give hope patients. Therefore, biomarker panel should generated potentially “at risk” individuals provide timely interventions better treatment outcomes patients soon possible.

Language: Английский

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Unraveling the Multifaceted Insights into Amyotrophic Lateral Sclerosis: Genetic Underpinnings, Pathogenesis, and Therapeutic Horizons

Mutation Research/Reviews in Mutation Research, Journal Year: 2024, Volume and Issue: 794, P. 108518 - 108518

Published: July 1, 2024

Language: Английский

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Role of vascular endothelial growth factor as a critical neurotrophic factor for the survival and physiology of motoneurons

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(8), P. 0 - 0

Published: Dec. 11, 2022

Vascular endothelial growth factor (VEGF) was discovered by its angiogenic activity. However, during evolution, it appeared earlier as a neurotrophic required for the development of nervous system in invertebrates lacking circulatory system. We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects neurons exposed to variety insults. Of particular interest is link established between and motoneurons, especially after design VEGFδ/δ mutant mice. These mice are characterized low levels develop muscle weakness motoneuron degeneration resembling amyotrophic lateral sclerosis. The administration through several routes animal models sclerosis delays motor impairment increases life expectancy. There new advances role physiology motoneurons. Our experimental aims use extraocular (abducens) motoneurons lesioned axotomy model studying actions. Axotomized abducens exhibit severe alterations their discharge activity loss synaptic boutons. exogenous axotomized either from transected nerve or intraventricularly, fully restores properties despite being axotomized. In addition, when an anti-VEGF neutralizing antibody delivered intact, uninjured these cells display pattern boutons resemble state axotomy. All data indicate essential

Language: Английский

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Microglia Influence Neurofilament Deposition in ALS iPSC-Derived Motor Neurons

Genes, Journal Year: 2022, Volume and Issue: 13(2), P. 241 - 241

Published: Jan. 27, 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motor neuron loss the primary phenotype, leading to muscle weakness wasting, respiratory failure, death. Although portion of ALS cases are linked one over 50 unique genes, vast majority sporadic nature. However, mechanisms underlying either familial or not entirely clear. Here, we used induced pluripotent stem cells derived from set identical twin brothers discordant for assess role astrocytes microglia on expression accumulation neurofilament proteins neurons. We found that neurons affected exhibited increased transcript levels all three isoforms phosphorylated puncta. further treatment with astrocyte-conditioned medium microglial-conditioned significantly impacted deposition. Together, these data suggest glial-secreted factors can alter pathology iPSC-derived

Language: Английский

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Riluzole–Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis

ACS Chemical Neuroscience, Journal Year: 2022, Volume and Issue: 13(15), P. 2252 - 2260

Published: July 22, 2022

Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, microglial activation. Inspired by reported clinical trial, we converted riluzole (1)–rasagiline (2) combination into single-molecule multi-target-directed ligands. By ligand-based approach, the highly structurally integrated hybrids 3–8 were designed synthesized. Through target- phenotypic-based screening pipeline, identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 μM) rationalized silico studies as well vitro brain permeability. using neuronal non-neuronal cell models, including ALS-patient-derived cells, disclosed for 6 neuroprotective/neuroinflammatory profile similar to that parent compounds their combination. Furthermore, unexpected MAO 1 8.7 might add piece puzzle its anti-ALS molecular profile.

Language: Английский

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Microstructural Changes in the Corpus Callosum in Neurodegenerative Diseases

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

The corpus callosum, the largest white matter structure in brain, plays a crucial role interhemispheric communication and cognitive function. This review examines microstructural changes observed callosum across various neurodegenerative diseases, including Alzheimer's disease, Parkinson's Huntington's amyotrophic lateral sclerosis (ALS). New neuroimaging studies, mainly those that use diffusion tensor imaging (DTI) advanced tractography methods, were put together to show how have happened organization of connections between them. Some most common ways breaks down are discussed, less fractional anisotropy, higher mean diffusivity, atrophy certain regions. relationship these decline, motor dysfunction, disease progression is explored. Additionally, we consider potential as biomarker for early detection monitoring. Studies people with disorders lower anisotropy diffusivity often specific disease. These happen before gray linked symptoms, which suggests could be used an sign neurodegeneration. also highlights implications findings understanding mechanisms developing therapeutic strategies. Future directions, application techniques longitudinal discussed elucidate degeneration processes. underscores importance pathophysiology diseases its target interventions.

Language: Английский

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Nanotechnological advancement for the treatment of neurodegenerative disorders

Journal of Dispersion Science and Technology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: Nov. 25, 2024

Language: Английский

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The mechanism of action of a novel neuroprotective low molecular weight dextran sulphate: New platform therapy for neurodegenerative diseases like Amyotrophic Lateral Sclerosis

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 30, 2022

Background: Acute and chronic neurodegenerative diseases represent an immense socioeconomic burden that drives the need for new disease modifying drugs. Common pathogenic mechanisms in these are evident, suggesting a platform neuroprotective therapy may offer effective treatments. Here we present evidence mode of pharmacological action novel low molecular weight dextran sulphate drug called ILB®. The working hypothesis was ILB® acts via activation heparin-binding growth factors (HBGF). Methods: Pre-clinical clinical (healthy people patients with ALS) vitro vivo studies evaluated In binding studies, functional assays gene expression analyses were followed by assessment effects animal model severe traumatic brain injury (sTBI) using analysis. Clinical data, to assess hypothesized action, also presented from early phase trials. Results: lengthened APTT time, acted as competitive inhibitor HGF-Glypican-3 binding, effected pulse release (HBGF) into circulation modulated factor signaling pathways. Gene analysis demonstrated substantial similarities dysregulation induced sTBI various human conditions supported cascading effect on activation, changes profound beneficial cellular functions affected diseases. transcriptional signature relevant cell survival, inflammation, glutamate signaling, metabolism synaptogenesis, consistent ability elevate circulating levels HGF models humans. Conclusion: releases, redistributes modulates bioactivity HBGF target compromised nervous tissues initiate cascade transcriptional, metabolic immunological control toxicity, normalize tissue bioenergetics, resolve inflammation improve function. This unique mechanism mobilizes naturally occurring repair restore homeostasis identified impact supports potential treat acute disease, including ALS.

Language: Английский

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