ArticleNature communications2017
Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 120 citations in OpenAlex.
- Article
- TDP-43 Acetylation at the Neuroimmune Interface: A Hypothesis-Driven Framework for Peripheral Inflammatory Stratotypes in ALS.Neurochemical research · 2026Review
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.BMC medicine · 2026Review
- Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration.Science (New York, N.Y.) · 2026Article
- Nuclear export modulates TDP-43 phase transition and cytoplasmic aggregation.bioRxiv : the preprint server for biology · 2026Article
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.Brain communications · 2026Review
- Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular-Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report.Diseases (Basel, Switzerland) · 2025Article
- TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins.Nature cell biology · 2025Article
- Genetic Variants inInternational journal of molecular sciences · 2025Article
- AIPred: comprehensive prediction and analysis of non-histone acetylation via protein language model and interpretable machine learning.BMC biology · 2025Article
- Brain Iron as a Surrogate Biomarker of Pathological TDP-43 Identifies Brain Region-Specific Signatures in Ageing, Alzheimer's Disease and Amyotrophic Lateral Sclerosis.bioRxiv : the preprint server for biology · 2025Article
- Histone deacetylase 9 modulates the acetylation dynamics of phototropin 1 to fine-tune phototropic responses in plants.Plant communications · 2025Article
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
TDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology. Analysis of functionally linked amyotrophic lateral sclerosis proteins revealed recruitment of p62, ubiquilin-2, and optineurin to TDP-43 aggregates. We demonstrate that TDP-43 acetylation-mimic pathology is potently suppressed by an HSF1-dependent mechanism that disaggregates TDP-43. Our study illustrates bidirectional TDP-43 processing in which TDP-43 aggregation is targeted by a coordinated chaperone response. Thus, activation or restoration of refolding mechanisms may alleviate TDP-43 aggregation in tissues that are uniquely susceptible to TDP-43 proteinopathies.TDP-43 aggregation is linked to various diseases including amyotrophic lateral sclerosis. Here the authors show that acetylation of the protein triggers TDP-43 pathology in cultured cells and mouse skeletal muscle, which can be cleared through an HSF1-dependent chaperone mechanism that disaggregates the protein.
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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.