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At least 19 recordsLinked to original sources
PubMed2026

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗
PubMed2026

Comparison of Proteomic Analysis of Cerebrospinal Fluid From Neurological Patients With and Without Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by progressive muscle weakness in both bulbar and extremity muscles, leading to a diverse clinical phenotype with motor and non-motor symptoms. Approximately 85% of ALS cases are sporadic (sALS), while the remaining 10%-15% are familial (fALS). Biological biomarkers of sporadic ALS remain poorly understood, hindering precise patient screening, delaying diagnosis and negatively affecting prognosis. This study aims to identify potential proteomic biomarkers by comparing the cerebrospinal fluid (CSF) of sALS patients with that of patients suffering from other neurological diseases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for proteomic profiling of CSF samples from 24 sALS patients and 26 patients with other neurological diseases. The complete protein expression profiles were compared using a two-tailed Student's t-test, with a p <&#x2009;0.05 considered statistically significant with additional FDR correction at the 0.1 level. Proteomic analysis of CSF samples identified significant quantitative changes in 96 proteins with threshold p&#x2009;<&#x2009;0.05 and 74 proteins with FDR <&#x2009;0.1 between sALS and non-ALS patients, including alterations in proteins associated with neurodegenerative processes, such as amyloid precursor proteins and inflammatory markers. CSF proteomic analysis reveals altered inflammatory and neurodegenerative metabolic pathways, providing valuable insights into the proteomic landscape of sALS. Several dysregulated proteins were consistent with the disease mechanisms highlighted in previous studies. These findings represent a step forward in developing personalised approaches for diagnosing and managing the disease.

Humans↗
PubMedDate not supplied

The otolaryngologic presentation of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a progressive dengenerative neuromuscular disease of insidious onset. It involves upper and lower motor neurons and causes both spastic and atrophic muscular symptoms. More than one fourth of patients have complaints relating to the head and neck (bulbar palsy); thus, the otolaryngologist may be the first physician to see them. Predominant symptoms are slurred speech, hoarseness, dysphagia, and dyspnea. Muscular weakness, atrophy, and fasciculation are noted on examination. The course is relentless, and only 20% of patients survive five years after diagnosis.

Adult↗
PubMed1977

Polio antibodies and HLA antigens in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive disease of the central nervous system. Its possible association with poliomyelitis was studied by measuring neutralizing antibodies against polio virus types 1, 2 and 3 in the sera and cerebrospinal fluids of 11 ALS-patients, but antibody titers did not markedly differ from those of the controls. The HLA antigens of 12 ALS patients were also determined, in order to reveal any possible genetically-determined susceptibility to the disease. Possible association of ALS with HLA-Bw40 was noted. In addition, the Bw40 antigen seemed to be associated with milder progression of the disease. The lymphocytes of the ALS patients seemed defective in their capacity to stimulate allogenic lymphocytes, possibly due to a relative decrease of B cells in the peripheral blood. Joint efforts of study groups of neuroepidemiology, immunology and genetics should be mobilized to reveal the true nature of these findings.

Aged↗
PubMed1978

[Thymus-dependent lymphocytes in multiple sclerosis and amyotrophic lateral sclerosis].

A study of the rosetteforming possibilities of T-lymphocytes in the peripheral blood of patients with disseminated sclerosis and lateral amyotrophical sclerosis detected a significant deficit of a subpopulation of T-cells, which form the most active rosettes of the morula type. Besides, in patients with disseminated sclerosis the relative amount of rosetteforming lymphocytes in the peripheral blood is significantly lower.

Adolescent↗
PubMed2026

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD&#xa0;=&#xa0;-0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD&#xa0;=&#xa0;-0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans↗
PubMed2026

Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with limited therapeutic options. The circulating metabolome comprises small molecules present in plasma/serum which are the intermediates and end-products of cellular metabolism, and is linked to ALS pathogenesis. METHODS: We conducted hypothesis-free two-sample Mendelian randomisation (MR) analysis of the concentration of 575 plasma/serum metabolites, to determine which are causally linked to risk of ALS. Significant metabolites were validated in an independent GWAS of plasma/serum metabolite concentrations and evaluated for sex-specific effects. Correlations between directly measured patient biofluid metabolite concentrations and ALS risk/severity were examined in 94 ALS patients and 40 controls. We experimentally assessed metabolic function in a murine neurons and human astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72. RESULTS: MR causally associated five metabolites with ALS risk after multiple-testing correction. Higher serum concentration of glycoprotein acetyls (P&#x2009;=&#x2009;9.7e&#x2009;-&#x2009;9, &#x3b2;&#x2009;=&#x2009;0.21) and the peptide DSGEGDFXAEGGGVR (P&#x2009;=&#x2009;8.0e&#x2009;-&#x2009;6, &#x3b2;&#x2009;=&#x2009;0.22) was associated with increased ALS risk, whereas higher plasma concentration of phenylalanylserine, isobutyrylcarnitine, and acetylcarnitine was protective (P&#x2009;<&#x2009;5e&#x2009;-&#x2009;5, &#x3b2;&#x2009;= -&#x2009;0.29 to&#x2009;-&#x2009;0.72). DSGEGDFXAEGGGVR has been linked to glucose metabolism but we have used genetic fine-mapping to link DSGEGDFXAEGGGVR, neuronal glucose uptake through GLUT3, and ALS risk. Direct measurement of metabolite concentrations in patient biofluids revealed elevated acetylcarnitine levels in patients with ALS, which were associated with delayed symptom onset (Cox regression, P&#x2009;=&#x2009;0.02, HR&#x2009;=&#x2009;0.4). Similarly, lactate is elevated in ALS patient CSF (ANOVA, P&#x2009;=&#x2009;1.3e&#x2009;-&#x2009;3) and in patients with longer survival time (Cox regression, P&#x2009;=&#x2009;0.03, HR&#x2009;=&#x2009;0.3). Plasma fructose is elevated in ALS patients with shorter survival time (Cox regression, P&#x2009;=&#x2009;0.02, HR&#x2009;=&#x2009;1.1). In vitro, neurons and astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72 demonstrated reduced metabolic flexibility. CONCLUSIONS: We provide evidence that impaired energy substrate availability contributes to ALS risk and severity. CNS cell types differ in their use of energy substrates and therefore we postulate the relative importance of different cell types for different stages of disease. Our findings support further investigation of metabolic interventions to treat or prevent ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2026

Integrated multi-omics identification of m6A-SNP-related diagnostic biomarkers in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks reliable and minimally invasive biomarkers for early diagnosis. m6A-associated single-nucleotide polymorphisms (m6A-SNPs) may influence RNA methylation and gene expression, offering opportunities to identify clinically relevant diagnostic markers. METHODS: We integrated eQTLGen cis-eQTL data, RMVar m6A-SNP annotations, and ALS transcriptomic datasets to identify m6A-SNP-related genes. Random Forest and LASSO regression were combined to screen robust diagnostic markers. A nomogram was constructed and validated using independent cohorts. Immune infiltration, predicted m6A modification sites, and potential RBP-SNP interactions were assessed. Peripheral blood samples from ALS patients were used for exploratory validation of gene expression and global m6A levels. RESULTS: We identified 109 ALS-associated m6A-SNP-related genes with cis-eQTL signals and narrowed these to seven candidate diagnostic markers (TMED5, OXR1, BRI3, FEM1C, SUZ12, EIF2AK4, and TJAP1). The seven-gene model outperformed the individual markers in the training cohort and retained moderate discrimination in the independent validation cohort. ALS samples showed differences in inferred immune-cell composition, including monocytes, neutrophils, and T-cell subsets. The selected SNP loci were located near predicted m6A sites and annotated RBP-binding regions. Exploratory clinical validation showed significant upregulation of FEM1C and SUZ12 at both mRNA and protein levels, accompanied by reduced global m6A modification. CONCLUSIONS: Through multi-omics integration and exploratory clinical validation, this study identifies m6A-SNP-related candidate markers associated with ALS. The findings support further evaluation of m6A-related signatures for ALS discrimination and molecular characterization, while larger independent cohorts and additional calibration are required before clinical application.

Humans↗
PubMed2025

Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable. OBJECTIVE: To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis. METHODS: The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method. RESULTS: We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR]&#x2009;=&#x2009;1.003; 95% confidence interval [95%CI]: 1.001-1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR&#x2009;=&#x2009;0.970; 95%CI: 0.956-0.984; p&#x2009;=&#x2009;1.96&#x2009;&#xd7;&#x2009;10-5; per 10-mmHg decrement). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS. CONCLUSION: In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.

Humans↗
PubMed1978

[Myelin toxicity of the serum of patients with amyotrophic lateral sclerosis in nerve tissue cultures].

In order to study the myelinotoxicity of the blood serum in patients with lateral amyotrophical sclerosis the authors used myelinated explants of the spinal cord of mice embryo. A total amount of 17 blood sera of patients with lateral amyotrophical sclerosis was studied. It was demonstrated that the serum of such patients introduced into nourishing medium in a concentration of 25% does not lead to an expressed demyelination of the nervous fibres. Cultivation of the spinal cord in a medium, containing 5--25% of the patient sera from the moment of explanation does not influence the process of myeline sheath formation. These data indicate that the serum of patients with lateral amyotrophical sclerosis do not possess myelinotoxic and myelininhibiting properties.

Adult↗
PubMed1979

[Muscle spasms in patients with amyotrophic lateral sclerosis (clinico-electromyographnic analysis)].

The diagnostic importance and electromyographic characteristics of the muscular spasms were studied in patients with lateral amyotrophic sclerosis at various stages of the disease. It has been shown that the muscular spasms are a typical symptom of this disease, and may be an early manifestation of the latter. The clinical and electromyographic characteristics of the spasms depend on the depth of the pathological process. Of importance in the origin of the muscular spasms in the lateral amyotrophic sclerosis is involvement of many levels of the cortico-muscular path, however, distrubances of the intraspinal mechanisms are, probably, the leading cause.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

[Aggravation following anaesthesia in a case of unknown lateral amyotrophic sclerosis (author's transl)].

A 66 year old man whose activity was almost normal underwent a lombar sympathectomy under general anesthesia (thiopental, gallamine, N2O). Immediately after recovery an acute respiratory distress became evident. It was due to a respiratory paralysis on which neostigmine had no effect. Neurologic examination showed the symptoms of an amyotrophic lateral sclerosis which had remained unknown so far. The respiratory paralysis persisted and one year later artificial ventilation is still necessary almost continuously. Two aspects of this very rare observation are discussed: first the cause and mecanisms of the aggravation of the neurologic disease following anesthesia, secondly the rather unusually important part played by the respiratory paralysis in this case of lateral amyotrophic sclerosis.

Acute Disease↗
PubMed1976

A family with amyotrophic lateral sclerosis and Parkinsonism.

Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) are known to occur simultaneously among some Chamorro inhabitants of Guam and other Mariana Islands (Stanhope et al., 1972). Outside of the Western Pacific Islands, the concurrence of ALS and PD seems to be rare. However, it has been observed to occur with sufficient frequency to suggest some causal association. The following is a report of a patient suffering from ALS whose family history included PD in several of the immediate relatives.

Amyotrophic Lateral Sclerosis↗
PubMed1979

Ballistic elbow flexion movements in patients with amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis made stereotyped 20 degrees elbow flexion movements as rapidly as possible while surface EMG was recorded from biceps and triceps. The characteristic ballistic movement EMG pattern could be recognised in almost all the patients. The first agonist burst and the first antagonist burst, which are normally limited in duration, were prolonged in patients with clinical signs of pyramidal tract disease or alpha motor neurone disease or both. Prolongation of these components permits the muscles to generate sufficient forces to accomplish the movements.

Adult↗