Heat Shock Proteins and the Regulation of Apoptosis

Abstract

nce the elucidation of their functions in protein folding and translocation, heat shock protein chaperones have been a target of research in all spheres of biomedicine. Within the last five years, research efforts have intensified, following the discovery of raised levels of heat shock protein (Hsp) expression in the brains of patients suffering from many neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington Disease and cerebral ischaemia. Expression of Hsps in the brains of patients is thought to form part of a general protective stress response. The stress in question, however, varies, depending on the particular disease. For example, accumulation of α-synuclein aggregates in Parkinson’s Disease causes stress to the protein folding machinery of the cells, with consequent up-regulation of stress proteins including Hsps. When markers indicative of the occurrence of apoptosis were also found in degenerating brain tissue, the question of how heat shock proteins might impact on apoptotic neural cells was raised. However, their particular function under diseased condi- tions remains unclear. This chapter highlights the involvement of Hsps in the regulation of neural apoptosis, from the original reports of Hsp expression during neurological disorders, to evidence of their neuroprotective properties and their potential as therapeutic molecules. Introduction