Heat Shock Proteins and Protein Quality Control in Alzheimer's Disease

Alzheimer's disease (AD) is a clinically and pathologically heterogeneous disorder. It is conceivable that a major part of this heterogeneity is due to less efficient protein quality control (PQC) systems, which normally serves as the safety guard in many conformational diseases. The chaperone machinery, largely consisting of heat shock proteins (HSPs), is central to PQC and guide protein folding, without being part of the final functional protein, but also assist in proper protein clearance, without actually being part of the degradation machinery. An efficient collaboration between HSPs and protein degradation systems is essential to maintain protein homeostasis. Here, we will review the literature on how HSPs are linked to protein degradation systems, and how this may interfere with Aβ and Tau pathology. Finally, we show how this basic research has led to the development of new ideas about the contribution of PQC to AD, in particular toward understanding initiating cellular factors and pathological protein seeding.