ArticleNature structural & molecular biology2021
TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 2 of them syntheses that pooled it.
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Who cites it
125 citing papers in PubMed, 2 syntheses or guidelines pooled it, 188 citations in OpenAlex.
- Neuroinflammation and Oxidative Stress in SOD1 Animal Models of ALS: A Meta-analysis Study of Their Effects on Disease Onset and Progression.Molecular neurobiology · 2026Pooled it
- L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.Nutrients · 2024Pooled it
- Mitochondrial DNA homeostasis: A novel therapeutic target for neurodegenerative diseases.Neural regeneration research · 2026Article
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- Pathogenicity Classification ofCells · 2026Article
- Structural-functional network decoupling in early stage amyotrophic lateral sclerosis reveals cell-type specific transcriptional signatures.BMC medicine · 2026Article
- Protein Disulfide Isomerase Disassembles TDP-43/G3BP1 Condensates and Antagonizes TDP-43 Pathological Aggregates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.Nature communications · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- TDP43 cytoplasmic mislocalization initiates mitochondrial dysfunction and intercellular senescence propagation in intervertebral disc degeneration.Experimental & molecular medicine · 2026Article
- Plasma isomiRs as Candidate Biomarkers for Amyotrophic Lateral Sclerosis.Neurology. Genetics · 2026Article
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- TDP-43-driven alternative splicing of UQCRC2 modulates mitochondrial bioenergetics.Biology direct · 2026Article
- Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation.International journal of molecular sciences · 2026Review
- Stabilized real-time Brillouin microscopy reveals fractal organization of protein condensates in living cells.Nature communications · 2026Article
- AGGRESCAN and its evolution: A two-decade perspective on protein aggregation prediction.Biophysical reviews · 2026Review
- From TDP-43/RNA complex formation to disease-linked TDP-43 aggregation through a structural and cellular approach.Nature communications · 2026Article
- Development and efficacy of ex vivo expanded autologous regulatory T cells for the treatment of amyotrophic lateral sclerosis.Frontiers in immunology · 2026Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) was initially thought to be associated with oxidative stress when it was first linked to mutant superoxide dismutase 1 (SOD1). The subsequent discovery of ALS-linked genes functioning in RNA processing and proteostasis raised the question of how different biological pathways converge to cause the disease. Both familial and sporadic ALS are characterized by the aggregation of the essential DNA- and RNA-binding protein TDP-43, suggesting a central role in ALS etiology. Here we report that TDP-43 aggregation in neuronal cells of mouse and human origin causes sensitivity to oxidative stress. Aggregated TDP-43 sequesters specific microRNAs (miRNAs) and proteins, leading to increased levels of some proteins while functionally depleting others. Many of those functionally perturbed gene products are nuclear-genome-encoded mitochondrial proteins, and their dysregulation causes a global mitochondrial imbalance that augments oxidative stress. We propose that this stress-aggregation cycle may underlie ALS onset and progression.
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Registered trials
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.