Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 377 - 377

Published: March 20, 2024

Amyotrophic lateral sclerosis (ALS) that comprises sporadic (sALS) and familial (fALS) cases, is a devastating neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle atrophy various clinical manifestations. However, the complex underlying mechanisms affecting this disease are not yet known. On other hand, there also no good prognosis due lack biomarkers therapeutic targets. Therefore, in study, means bioinformatics analysis, sALS-affected tissue was analyzed using GEO GSE41414 dataset, identifying 397 differentially expressed genes (DEGs). Functional analysis revealed 320 up-regulated DEGs associated with development 77 down-regulated linked energy metabolism. Protein–protein interaction network identified 20 hub genes, including EIF4A1, HNRNPR NDUFA4. Furthermore, miRNA target gene networks 17 miRNAs hsa-mir-206, hsa-mir-133b hsa-mir-100-5p having been previously implicated ALS. This study presents new potential targets for ALS correlating information obtained comprehensive literature review, providing their role

Language: Английский

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Current potential pathogenic mechanisms of copper-zinc superoxide dismutase 1 (SOD1) in amyotrophic lateral sclerosis

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: 35(5), P. 549 - 563

Published: Feb. 21, 2024

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN LMN) innervating the muscles of trunk, extremities, head, neck face in cerebrum, brain stem spinal cord, results progressive weakness, atrophy fasciculation muscle innervated by related UMN LMN, accompanying with pathological signs leaded cortical tract lesion. The pathogenesis about ALS not fully understood, no specific drugs are available to cure prevent progression this at present. In review, we reviewed structure associated functions copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 crucial ALS, outline pathogenic mechanisms that have been identified recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative axonal transport disruption, prion-like propagation, non-cytologic toxicity glial cells. This review will help us deeply understand current field ALS.

Language: Английский

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Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the national ALS Registry

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 6

Published: Jan. 3, 2025

To estimate the projected number of ALS cases in United States from 2022 to 2030. Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no known cure. Because not notifiable States, accurate ascertainment prevalent continues be challenge. overcome this, National Registry (Registry) uses novel methods newly diagnosed existing States.

Language: Английский

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Edaravone Improves Motor Dysfunction Following Brachial Plexus Avulsion Injury in Rats

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Brachial plexus root avulsion (BPRA) is often caused by road collisions, leading to total loss of motor function in the upper limb. At present, effective treatment options remain limited. Edaravone (EDA), a substance that eliminates free radicals, exhibits numerous biological properties, including neuroprotective, antioxidant and anti-inflammatory effects. However, specific role molecular mechanisms EDA BPRA be fully elucidated. The present study used rat model BPRA, following fifth, sixth seventh cervical (C5, C6 C7) anterior roots. Notably, was replanted subcutaneous injection either saline or 30 mg/kg/day for seven continuous days. Subsequently, behavioral, histochemical, Western blot reverse transcription-quantitative PCR (RT-PCR) analyses were conducted. Results revealed with improves dysfunction, indicated increased Grooming test score, usage affected limb, Irvine, Beatties Bresnahan (IBB) BPRA. In addition, reduced death motoneurons (MNs), number Nissl-positive neuron, at site inhibited neuroinflammation cellular pyroptosis, decreased expression levels IL-1β, IL-6, TNF-α, IL-18, p-p65, NLRP3, GSDMD Caspase-1, improved morphology abnormal myocutaneous nerve fibers, promoted axon remyelination, mRNA remyelination-associated genes, egr2, GAP-43, hmgcr, L1CAM, mpz, pmp22 prx demyelination-associated ngfr, notch1, pou3f1 sox2, alleviated muscle atrophy, weight volume biceps brachii muscle, fibroblasts diameters fibers. Collectively, results suggested may support axonal remyelination inhibit pyroptosis-associated neuroinflammation, enhancing MN survival facilitating functional recovery. Thus, provide novel theoretical basis use

Language: Английский

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Synthesis and Study of Anticonvulsant, Anti-Ischemic, and Antihypoxic Activity of NMDA and AMPA Dicationic Adamantane-Containing Open Channel Blockers In Vitro and In Vivo

Pharmaceutical Chemistry Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Language: Английский

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Progressive Bulbar Palsy (PBP) or Bulbar Onset MND: “A Case Report”

Journal of Pharmacy And Bioallied Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

A BSTRACT patient with enhancing bulbar palsy, a type of efferent neuron disease that causes hypertrophy and twitching the tongue’s musculature, dysphagia, dysarthria, an excessive buildup secretions, is described. Enhancing palsy degenerative disorder nuclei in medulla. The may consult dentist at first. Clinicians must possess knowledge regarding telltale signs symptoms this terminal illness to promptly refer patients for neurologic evaluation initiate appropriate symptomatic treatments.

Language: Английский

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Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4228 - 4228

Published: April 29, 2025

Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H2O2 and O2. This detoxification process, essential for cellular homeostasis, relies on precisely orchestrated catalytic mechanism involving the copper cation, while zinc cation contributes to structural integrity of enzyme. study presents 2.3 Å crystal structure human SOD1 (PDB ID: 9IYK), revealing an assembly six homodimers twelve distinct active sites. The water molecules form complex hydrogen-bonding network drives proton transfer sustains site dynamics. Our also uncovers subtle conformational changes highlight intrinsic flexibility SOD1, which its function. Additionally, we observe how these dynamic features may be linked pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding hSOD1's mechanistic intricacies influence coordination, this offers valuable insights developing therapeutic strategies targeting ALS. structure's unique conformations interactions illuminate new facets hSOD1 function, underscoring critical role dynamics in catalysis. Moreover, conducted molecular docking analysis using potential radical scavengers Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors misfolded aggregation along stress apoptosis, respectively. results showed CHEMBL1075867, free scavenger derivative, most promising at binding hSOD1, highlighting further studies against SOD1-mediated

Language: Английский

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Pathological mechanisms of amyotrophic lateral sclerosis

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(5), P. 1036 - 1044

Published: Aug. 14, 2023

Abstract Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system, cause of which remains unexplained despite several years research. Thus, journey understanding or treating amyotrophic is still long one. According current research, likely not due single factor but rather combination mechanisms mediated by complex interactions between molecular and genetic pathways. The progression involves multiple cellular processes interaction different makes it difficult identify causative factors sclerosis. Here, we review most common sclerosis-associated pathogenic genes pathways involved in sclerosis, as well summarize currently proposed potential responsible for their evidence involvement In addition, discuss emerging strategies treatment Studying emergence these new therapies may help further our disease.

Language: Английский

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Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Dec. 12, 2023

Background The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the simplex virus (HSV), varicella-zoster (VZV), Epstein–Barr (EBV), cytomegalovirus (CMV), HHV-6, HHV-7 ALS through a bidirectional Mendelian randomization (MR) method. Methods genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, median, simple mode, mode methods. MR-Egger intercept test, MR-PRESSO Cochran’s Q funnel plots, leaveone-out analysis used to verify validity robustness of MR results. Results In forward IVW, genetically predicted HSV [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685–1.0154; p 0.4886], keratitis keratoconjunctivitis (OR 0.9897; CI: 0.9739–1.0059; 0.2107), anogenital infection 1.0062; 0.9826–1.0304; 0.6081), VZV IgG 1.0003; 0.9849–1.0160; 0.9659), EBV 0.9509; 0.8879–1.0183; 0.1497), CMV 0.9481; 0.8680–1.0357; 0.2374), HHV-6 0.9884; 0.9486–1.0298; 0.5765) 0.9991; 0.9693–1.0299; 0.9557) not causally associated ALS. reverse IVW revealed comparable findings, indicating no link HHVs reliability findings verified sensitivity analysis. Conclusion According study, there is evidence (HSV, VZV, EBV, CMV, HHV-7)

Language: Английский

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Current Therapy in Amyotrophic lateral sclerosis (ALS): a review on Past and Future Therapeutic Strategies

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 272, P. 116496 - 116496

Published: May 13, 2024

Language: Английский

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