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Role of heat shock proteins during polyglutamine neurodegeneration: mechanisms and hypothesis

Role of heat shock proteins during polyglutamine neurodegeneration: mechanisms and hypothesis
Role of heat shock proteins during polyglutamine neurodegeneration: mechanisms and hypothesis
A common feature of many neurodegenerative diseases, including Alzheimer's and Parkinsons's disease, the prion disorders, and the CAG repeat polyglutamine (polyQ) diseases, is the occurrence of protein aggregates within or outside of nerve cells. Molecular chaperones such as heat shock proteins (HSPs) have been proposed to play a critical role in preventing the accumulation of misfolded proteins that lead to the deposition of aggregates during pathology. This article focuses on the role of HSPs during polyQ pathologies, which include Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral and pallidoluysian atrophy, and several forms of spinocerebellar ataxia. Recently, unifying mechanisms that are involved during polyQ disease have emerged, such as abnormal transcription, impaired degradation systems, and interference of a polyQ expansion with neuronal survival and death-signaling pathways like the activation of caspases and kinases. This article reviews recent studies that point to the involvement of these mechanisms during polyQ pathology and discusses how HSPs can interfere with such processes by paying special attention to HSPs as modulators of survival and death-signaling pathways.
polyglutamine, heat shock protein, cell death, protein aggregation, transcription, proteasome, autophagy
0895-8696
69-9^
Wyttenbach, Andreas
05019897-52b1-4bb6-b259-5d51abae7540
Wyttenbach, Andreas
05019897-52b1-4bb6-b259-5d51abae7540

Wyttenbach, Andreas (2004) Role of heat shock proteins during polyglutamine neurodegeneration: mechanisms and hypothesis. Journal of Molecular Neuroscience, 23 (1-2), 69-9^.

Record type: Article

Abstract

A common feature of many neurodegenerative diseases, including Alzheimer's and Parkinsons's disease, the prion disorders, and the CAG repeat polyglutamine (polyQ) diseases, is the occurrence of protein aggregates within or outside of nerve cells. Molecular chaperones such as heat shock proteins (HSPs) have been proposed to play a critical role in preventing the accumulation of misfolded proteins that lead to the deposition of aggregates during pathology. This article focuses on the role of HSPs during polyQ pathologies, which include Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral and pallidoluysian atrophy, and several forms of spinocerebellar ataxia. Recently, unifying mechanisms that are involved during polyQ disease have emerged, such as abnormal transcription, impaired degradation systems, and interference of a polyQ expansion with neuronal survival and death-signaling pathways like the activation of caspases and kinases. This article reviews recent studies that point to the involvement of these mechanisms during polyQ pathology and discusses how HSPs can interfere with such processes by paying special attention to HSPs as modulators of survival and death-signaling pathways.

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More information

Published date: April 2004
Keywords: polyglutamine, heat shock protein, cell death, protein aggregation, transcription, proteasome, autophagy

Identifiers

Local EPrints ID: 56087
URI: http://eprints.soton.ac.uk/id/eprint/56087
ISSN: 0895-8696
PURE UUID: 86f0d79d-20e8-4a63-b924-e24b3f85be37

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Date deposited: 07 Aug 2008
Last modified: 08 Jan 2022 04:02

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Contributors

Author: Andreas Wyttenbach

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