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.
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