The Role of Heat Shock Proteins during Neurodegeneration in Alzheimer’s, Parkinson’s and Huntington’s Disease

Abstract

A number of acute and chronic neurodegenerative conditions are associated by protein misfolding and aggregation of proteins within and outside cells. Misfolded proteins and protein aggregation are controlled by molecular chaperones such as heat shock proteins (HSPs) that are constitutively and inducibly expressed in the nervous system. There is increasing evidence that HSPs could counteract common pathological mechanisms that take place during Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). This is achieved by HSPs either interfering with the misfolded disease proteins preventing unwanted interactions with other cellular proteins and/or by reducing the risk of formation of toxic oligomeric assemblies of the respective disease proteins such as tau and amyloid-β in AD, α-synuclein in PD and huntingtin in HD. But HSPs are also expected to interfere with detrimental processes that occur during these diseases including oxidative stress and abnormal activation of signaling pathways or act supportive towards degradation systems such as the ubiquitin proteasome- and the autophagic-lysosomal pathway. Specific neuronal structures such as synapses and axons also harbour HSPs that may be misregulated during the disease process. Hence HSPs are expected to be critically involved in the progression of AD, PD and HD making them potential therapeutic targets and the studies discussed in this chapter support this view.