Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

Abstract

This review will analyze growing evidence suggesting a convergence between two major areas of research: Alzheimer’s disease (AD) and chaperonopathies. While AD is a widely recognized medical, public health, and social problem, the chaperonopathies have not yet been acknowledged as a related burden of similar magnitude. However, recent evidence collectively indicates that such possibility exists in that AD, or at least some forms of it, may indeed be a chaperonopathy. The importance of considering this possibility cannot be overemphasized since it provides a novel point of view to examine AD and potentially suggests new therapeutic avenues. In this review, we focus on the mitochondrial chaperone HSP60 and discuss some of its biological, molecular, and pathological facets as they pertain to AD. We further illustrate how HSP60 may be an etiologic-pathogenic factor in AD and, as such, it could become a novel, effective therapeutic target. This possibility is discussed both in the light of negative chaperonotherapy, namely the development of means to inhibit HSP60 in the event its excessive activity is a disease-promoting event in AD, as well as positive chaperonotherapy, that is boosting its activity if, on the other hand, it is demonstrated that HSP60 insufficiency is a key feature of AD with such pathological consequences as causing mitochondrial dysfunction.