ArticleHuman molecular genetics2014
Prion-like nuclear aggregation of TDP-43 during heat shock is regulated by HSP40/70 chaperones.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 157 citations in OpenAlex.
- FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.EMBO reports · 2026Article
- Review
- Human chaperone DNAJB6b suppresses tau fibril formation through co-aggregation.Communications chemistry · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Kinetics and Spatial Distribution of β-Sheet Development in TDP-43ACS chemical neuroscience · 2026Article
- DNAJB6: A guardian against neurodegeneration.Neural regeneration research · 2026Article
- Emw1/TTC27 is a chaperone required for folding of the eukaryotic elongation factor 2.Cellular and molecular life sciences : CMLS · 2026Article
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Amyloidogenic oligomers derived from TDP-43 LCD promote the condensation and phosphorylation of TDP-43.Chemical science · 2026Article
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- Biomolecular condensates: molecular structure, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Effects of solution conditions on the self-assembly of the chaperone protein DNAJB6b.Communications chemistry · 2025Article
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- The Role of α-Synuclein-DNAJB6b Coaggregation in Amyloid Suppression.ACS chemical neuroscience · 2025Article
- Proteomics Analysis of the TDP-43 Interactome in Cellular Models of ALS Pathogenesis.Journal of neurochemistry · 2025Article
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Reduced dynamicity and increased high-order protein assemblies in dense fibrillar component of the nucleolus under cellular senescence.Redox biology · 2024Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
TDP-43 aggregation in the cytoplasm or nucleus is a key feature of the pathology of amyotrophic lateral sclerosis and frontotemporal dementia and is observed in numerous other neurodegenerative diseases, including Alzheimer's disease. Despite this fact, the inciting events leading to TDP-43 aggregation remain unclear. We observed that endogenous TDP-43 undergoes reversible aggregation in the nucleus after the heat shock and that this behavior is mediated by the C-terminal prion domain. Substitution of the prion domain from TIA-1 or an authentic yeast prion domain from RNQ1 into TDP-43 can completely recapitulate heat shock-induced aggregation. TDP-43 is constitutively bound to members of the Hsp40/Hsp70 family, and we found that heat shock-induced TDP-43 aggregation is mediated by the availability of these chaperones interacting with the inherently disordered C-terminal prion domain. Finally, we observed that the aggregation of TDP-43 during heat shock led to decreased binding to hnRNPA1, and a change in TDP-43 RNA-binding partners suggesting that TDP-43 aggregation alters its function in response to misfolded protein stress. These findings indicate that TDP-43 shares properties with physiologic prions from yeast, in that self-aggregation is mediated by a Q/N-rich disordered domain, is modulated by chaperone proteins and leads to altered function of the protein. Furthermore, they indicate that TDP-43 aggregation is regulated by chaperone availability, explaining the recurrent observation of TDP-43 aggregates in degenerative diseases of both the brain and muscle where protein homeostasis is disrupted.
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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.