ArticleMolecular neurodegeneration2011
C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 109 citations in OpenAlex.
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- Oxidative stress and inflammation in neurodegenerative disorders.Archives of toxicology · 2026Review
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation.bioRxiv : the preprint server for biology · 2025Article
- Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.Cell reports · 2025Article
- The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.Annals of neurology · 2024Review
- Molecular hallmarks of ageing in amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2024Review
- Article
- Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation.Molecular neurobiology · 2023Article
- Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools.Pharmaceutics · 2023Review
- Understanding In Vitro Pathways to Drug Discovery for TDP-43 Proteinopathies.International journal of molecular sciences · 2022Article
- Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376DBrain communications · 2022Article
- Review
- Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment.International journal of molecular sciences · 2021Article
- Mitogen-Activated Protein Kinase Pathway in Amyotrophic Lateral Sclerosis.Biomedicines · 2021Review
- The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS.International journal of molecular sciences · 2021Review
- Mechanisms of TDP-43 Proteinopathy Onset and Propagation.International journal of molecular sciences · 2021Review
- Prion-like C-Terminal Domain of TDP-43 and α-Synuclein Interact Synergistically to Generate Neurotoxic Hybrid Fibrils.Journal of molecular biology · 2021Article
- The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS.Antioxidants (Basel, Switzerland) · 2021Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTDP-43 proteinopathies are characterized by loss of nuclear TDP-43 expression and formation of C-terminal TDP-43 fragmentation and accumulation in the cytoplasm. Recent studies have shown that TDP-43 can accumulate in RNA stress granules (SGs) in response to cell stresses and this could be associated with subsequent formation of TDP-43 ubiquinated protein aggregates. However, the initial mechanisms controlling endogenous TDP-43 accumulation in SGs during chronic disease are not understood. In this study we investigated the mechanism of TDP-43 processing and accumulation in SGs in SH-SY5Y neuronal-like cells exposed to chronic oxidative stress. Cell cultures were treated overnight with the mitochondrial inhibitor paraquat and examined for TDP-43 and SG processing.
resultsWe found that mild stress induced by paraquat led to formation of TDP-43 and HuR-positive SGs, a proportion of which were ubiquitinated. The co-localization of TDP-43 with SGs could be fully prevented by inhibition of c-Jun N-terminal kinase (JNK). JNK inhibition did not prevent formation of HuR-positive SGs and did not prevent diffuse TDP-43 accumulation in the cytosol. In contrast, ERK or p38 inhibition prevented formation of both TDP-43 and HuR-positive SGs. JNK inhibition also inhibited TDP-43 SG localization in cells acutely treated with sodium arsenite and reduced the number of aggregates per cell in cultures transfected with C-terminal TDP-43 162-414 and 219-414 constructs.
conclusionsOur studies are the first to demonstrate a critical role for kinase control of TDP-43 accumulation in SGs and may have important implications for development of treatments for FTD and ALS, targeting cell signal pathway control of TDP-43 aggregation.
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Registered trials
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