ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1999
Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it, 428 citations in OpenAlex.
- NeuroGeM, a knowledgebase of genetic modifiers in neurodegenerative diseases.BMC medical genomics · 2013Pooled it
- Transcriptome Analysis Revealed the Copper Ion Uptake by Oocystis borgei from Offshore Polluted Water.Marine biotechnology (New York, N.Y.) · 2025Article
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease.Neurobiology of disease · 2025Article
- The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.Cerebellum (London, England) · 2024Review
- Spermidine treatment: induction of autophagy but also apoptosis?Molecular brain · 2024Article
- The roles of HSP40/DNAJ protein family in neurodegenerative diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Protective Role of Capsaicin in Neurological Disorders: An Overview.Neurochemical research · 2022Review
- Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease.Disease models & mechanisms · 2022Article
- Analysis of Huntington's Disease Modifiers Using the Hyperbolic Mapping of the Protein Interaction Network.International journal of molecular sciences · 2022Article
- Modifier pathways in polyglutamine (PolyQ) diseases: from genetic screens to drug targets.Cellular and molecular life sciences : CMLS · 2022Review
- Plasma PolyQ-ATXN3 Levels Associate With Cerebellar Degeneration and Behavioral Abnormalities in a New AAV-Based SCA3 Mouse Model.Frontiers in cell and developmental biology · 2022Article
- Article
- Mutant Ataxin-3-Containing Aggregates (MATAGGs) in Spinocerebellar Ataxia Type 3: Dynamics of the Disorder.Molecular neurobiology · 2021Review
- RACK1 modulates polyglutamine-induced neurodegeneration by promoting ERK degradation in Drosophila.PLoS genetics · 2021Article
- A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3.Cell death & disease · 2021Article
- Ubiquilin-2 differentially regulates polyglutamine disease proteins.Human molecular genetics · 2020Article
- Pathogenesis of SCA3 and implications for other polyglutamine diseases.Neurobiology of disease · 2020Review
- Challenging Proteostasis: Role of the Chaperone Network to Control Aggregation-Prone Proteins in Human Disease.Advances in experimental medicine and biology · 2020Review
- Determining the Fate of Neurons in SCA3: ATX3, a Rising Decision Maker in Response to DNA Stresses and Beyond.Frontiers in cell and developmental biology · 2020Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyglutamine (polygln) diseases are a group of inherited neurodegenerative disorders characterized by protein misfolding and aggregation. Here, we investigate the role in polygln disease of heat shock proteins (Hsps), the major class of molecular chaperones responsible for modulating protein folding in the cell. In transfected COS7 and PC12 neural cells, we show that Hsp40 and Hsp70 chaperones localize to intranuclear aggregates formed by either mutant ataxin-3, the disease protein in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), or an unrelated green fluorescent protein fusion protein containing expanded polygln. We further demonstrate that expression of expanded polygln protein elicits a stress response in cells as manifested by marked induction of Hsp70. Studies of SCA3/MJD disease brain confirm these findings, showing localization of Hsp40 and, less commonly, Hsp70 chaperones to intranuclear ataxin-3 aggregates. In transfected cells, overexpression of either of two Hsp40 chaperones, the DNAJ protein homologs HDJ-1 and HDJ-2, suppresses aggregation of truncated or full-length mutant ataxin-3. Finally, we extend these studies to a PC12 neural model of polygln toxicity in which we demonstrate that overexpression of HDJ-1 suppresses polygln aggregation with a parallel decrease in toxicity. These results suggest that expanded polygln protein induces a stress response and that specific molecular chaperones may aid the handling of misfolded or aggregated polygln protein in neurons. This study has therapeutic implications because it suggests that efforts to increase chaperone activity may prove beneficial in this class of diseases.
Indexed as
Identifiers
10575031PMC6782415W2132513906What OpenQuestion holds
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.