Abstract
Heat shock proteins are members of a large family that function normally in nascent protein folding and the removal of damaged proteins and are able to respond to cellular stresses such as thermal insult to prevent catastrophic protein aggregation. A number of the most common neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases are characterized by such abnormal protein folding and aggregation, and the induction of the heat shock response is observed in these cases through their increased expression and often localization within the inclusions. Tau proteins form the major structural component of the neurofibrillary protein aggregates that correlate with cognitive decline in Alzheimer’s disease, and appropriately this abnormal tau is targeted for corrective action by the heat shock proteins that recognize sequence motifs that are normally masked though microtubule binding. This specific heat shock response to the formation of abnormal tau can also be targeted pharmacologically to inhibit the refolding pathways and drive the degradation of tau species that are thought to be pathogenic. This review discusses the recent advances of the roles of heat shock proteins in this process.
Keywords: Heat shock proteins, neurodegeneration, aggregation, chaperones, proteasome, ubiquitin, autophagy, tau protein.
Current Alzheimer Research
Title:Targeting Heat Shock Proteins in Tauopathies
Volume: 7 Issue: 8
Author(s): M. DeTure, C. Hicks and L. Petrucelli
Affiliation:
Keywords: Heat shock proteins, neurodegeneration, aggregation, chaperones, proteasome, ubiquitin, autophagy, tau protein.
Abstract: Heat shock proteins are members of a large family that function normally in nascent protein folding and the removal of damaged proteins and are able to respond to cellular stresses such as thermal insult to prevent catastrophic protein aggregation. A number of the most common neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases are characterized by such abnormal protein folding and aggregation, and the induction of the heat shock response is observed in these cases through their increased expression and often localization within the inclusions. Tau proteins form the major structural component of the neurofibrillary protein aggregates that correlate with cognitive decline in Alzheimer’s disease, and appropriately this abnormal tau is targeted for corrective action by the heat shock proteins that recognize sequence motifs that are normally masked though microtubule binding. This specific heat shock response to the formation of abnormal tau can also be targeted pharmacologically to inhibit the refolding pathways and drive the degradation of tau species that are thought to be pathogenic. This review discusses the recent advances of the roles of heat shock proteins in this process.
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Cite this article as:
DeTure M., Hicks C. and Petrucelli L., Targeting Heat Shock Proteins in Tauopathies, Current Alzheimer Research 2010; 7 (8) . https://dx.doi.org/10.2174/156720510793611565
DOI https://dx.doi.org/10.2174/156720510793611565 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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