ArticleHuman molecular genetics2010
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 138 citations in OpenAlex.
- Proteomic analysis of cerebrospinal fluid of amyotrophic lateral sclerosis patients in the presence of autologous bone marrow derived mesenchymal stem cells.Stem cell research & therapy · 2024Trial
- A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.Life science alliance · 2026Article
- Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.Scientific reports · 2025Article
- Meta-Analysis of Gene Expression in Bulk-Processed Post-Mortem Spinal Cord from ALS Patients and Normal Controls.NeuroSci · 2025Article
- Neuromuscular dysfunction in patient-derived FUSNAR molecular medicine · 2025Article
- Inflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model.Science advances · 2024Article
- KIF1A, R1457Q, and P1688L Mutations Induce Protein Abnormal Aggregation and Autophagy Impairment in iPSC-Derived Motor Neurons.Biomedicines · 2024Article
- Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation.JCI insight · 2024Article
- TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.Cell reports · 2024Article
- Meta-analysis of differential gene expression in lower motor neurons isolated by laser capture microdissection from post-mortem ALS spinal cords.Frontiers in genetics · 2024Article
- Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Article
- Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increasedFrontiers in cell and developmental biology · 2023Article
- Identifying Candidate Genes Associated with Sporadic Amyotrophic Lateral Sclerosis via Integrative Analysis of Transcriptome-Wide Association Study and Messenger RNA Expression Profile.Cellular and molecular neurobiology · 2023Article
- Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of neurological disorders-associated genemicroPublication biology · 2023Article
- Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis.Acta neuropathologica · 2022Article
- Singling out motor neurons in the age of single-cell transcriptomics.Trends in genetics : TIG · 2022Review
- Discovery of Phospholipase D Inhibitors with Improved Drug-like Properties and Central Nervous System Penetrance.ACS medicinal chemistry letters · 2022Article
- Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons.Stem cell reports · 2021Article
- Nuclear depletion of RNA-binding protein ELAVL3 (HuC) in sporadic and familial amyotrophic lateral sclerosis.Acta neuropathologica · 2021Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (P <or= 10(-3)) and 411 aberrantly spliced genes (P <or= 10(-5)). The aberrantly spliced genes were highly enriched in cell adhesion (P <or= 10(-57)), especially cell-matrix as opposed to cell-cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell-matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration. Data deposition: GeneChip raw data (CEL-files) have been deposited for public access in the Gene Expression Omnibus (GEO), www.ncbi.nlm.nih.gov/geo, accession number GSE18920.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.