ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Loss of Hsp70 exacerbates pathogenesis but not levels of fibrillar aggregates in a mouse model of Huntington's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. 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, 107 citations in OpenAlex.
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS.International journal of molecular sciences · 2023Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Lack of Hikeshi activates HSF1 activity under normal conditions and disturbs the heat-shock response.Life science alliance · 2022Article
- Heat-shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition.Nature cell biology · 2022Article
- Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease.Disease models & mechanisms · 2022Article
- Modifier pathways in polyglutamine (PolyQ) diseases: from genetic screens to drug targets.Cellular and molecular life sciences : CMLS · 2022Review
- Heat shock proteins and the calcineurin-crz1 signaling regulate stress responses in fungi.Archives of microbiology · 2022Review
- Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeutic Interventions.Biomedicines · 2021Review
- From Seeds to Fibrils and Back: Fragmentation as an Overlooked Step in the Propagation of Prions and Prion-Like Proteins.Biomolecules · 2020Review
- Targeting Hsp70 facilitated protein quality control for treatment of polyglutamine diseases.Cellular and molecular life sciences : CMLS · 2020Review
- Expression of Heat Shock Protein 70 Is Insufficient To ExtendG3 (Bethesda, Md.) · 2019Article
- Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein.Nature neuroscience · 2019Article
- Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Review
- Cell-Autonomous and Non-cell-Autonomous Pathogenic Mechanisms in Huntington's Disease: Insights from In Vitro and In Vivo Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Longitudinal monitoring of mesoscopic cortical activity in a mouse model of microinfarcts reveals dissociations with behavioral and motor function.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Molecular mechanisms of proteinopathies across neurodegenerative disease: a review.Neurological research and practice · 2019Review
- SIRT3 Regulation of Mitochondrial Quality Control in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2019Article
- Targeting the proteostasis network in Huntington's disease.Ageing research reviews · 2019Review
- TSPO-PET imaging using [18F]PBR06 is a potential translatable biomarker for treatment response in Huntington's disease: preclinical evidence with the p75NTR ligand LM11A-31.Human molecular genetics · 2018Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Endogenous protein quality control machinery has long been suspected of influencing the onset and progression of neurodegenerative diseases characterized by accumulation of misfolded proteins. Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expansion of a polyglutamine (polyQ) tract in the protein huntingtin (htt), which leads to its aggregation and accumulation in inclusion bodies. Here, we demonstrate in a mouse model of HD that deletion of the molecular chaperones Hsp70.1 and Hsp70.3 significantly exacerbated numerous physical, behavioral and neuropathological outcome measures, including survival, body weight, tremor, limb clasping and open field activities. Deletion of Hsp70.1 and Hsp70.3 significantly increased the size of inclusion bodies formed by mutant htt exon 1, but surprisingly did not affect the levels of fibrillar aggregates. Moreover, the lack of Hsp70s significantly decreased levels of the calcium regulated protein c-Fos, a marker for neuronal activity. In contrast, deletion of Hsp70s did not accelerate disease in a mouse model of infectious prion-mediated neurodegeneration, ruling out the possibility that the Hsp70.1/70.3 mice are nonspecifically sensitized to all protein misfolding disorders. Thus, endogenous Hsp70s are a critical component of the cellular defense against the toxic effects of misfolded htt protein in neurons, but buffer toxicity by mechanisms independent of the deposition of fibrillar aggregates.
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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.