Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS subjects (8,224 AS and 1,437 APA), including changes in ALS-associated genes (for example, ATXN2 and FUS), and in subjects with sporadic ALS (sALS; 2,229 AS and 716 APA). Furthermore, heterogeneous nuclear ribonucleoprotein H (hnRNPH) and other RNA-binding proteins are predicted to be potential regulators of cassette exon AS events in both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830686 | PMC |
| http://dx.doi.org/10.1038/nn.4065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ATXN2 polyglutamine intermediate repeats length expansions in Malaysian patients with amyotrophic lateral sclerosis (ALS).
Neurogenetics
January 2025
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
Intermediate CAG repeats from 29 to 33 in the ATXN2 gene contributes to the risk of amyotrophic lateral sclerosis (ALS) in European and Asian populations. In this study, 148 ALS patients of multiethnic descent: Chinese (56.1%), Malay (24.
View Article and Find Full Text PDFMachine learning identified novel players in lipid metabolism, endosomal trafficking, and iron metabolism of the ALS spinal cord.
Sci Rep
January 2025
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Although genes causing familial cases have been identified, those of sporadic ALS, which occupies the majority of patients, are still elusive. In this study, we adopted machine learning to build binary classifiers based on the New York Genome Center (NYGC) ALS Consortium's RNA-seq data of the postmortem spinal cord of ALS and non-neurological disease control.
View Article and Find Full Text PDFInteraction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis.
Ann Clin Transl Neurol
January 2025
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, USA.
Objective: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).
Methods: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates.
Exploring the Role of Variants in Italian ALS Patients.
Genes (Basel)
December 2024
Centro Clinico NeMO Adulti, Fondazione Serena Onlus-Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Variants in Cyclin F () have been associated to amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) in a group of cases. The objectives of this study were to determine the contribution of in a large cohort of Italian ALS patients, to look for genotype-phenotype correlation of the mutations and to evaluate the -associated clinical features. We applied next-generation sequencing technologies on 971 unrelated Italian ALS patients and we filtered results to look for variants in gene.
View Article and Find Full Text PDFAutophagy receptor-inspired chimeras: a novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation.
J Zhejiang Univ Sci B
September 2024
Institute of Pharmaceutical Pharmacology, School of Pharmacy, University of South China, Hengyang 421001, China.
Neurodegenerative diseases (NDDs), mainly including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD), are sporadic and rare genetic disorders of the central nervous system. A key feature of these conditions is the slow accumulation of misfolded protein deposits in brain neurons, the excessive aggregation of which leads to neurotoxicity and further disorders of the nervous system.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!