Exploring the Role of Hsp60 in Alzheimer’s Disease and Type 2 Diabetes: Suggestion for Common Drug Targeting

Abstract

Heat shock protein 60 (Hsp60) is a member of the chaperonin family of heat shock proteins (HSPs), primarily found in the mitochondrial matrix. As a molecular chaperone, Hsp60 plays an essential role in mediating protein folding and assembly, and together with the co-chaperon Hsp10, it is thought to maintain protein homeostasis. Recently, it has been found to localize in non-canonical, extra-mitochondrial sites such as cell membranes or extracellular fluids, particularly in pathological conditions. Starting from its biological function, this review aims to provide a comprehensive understanding of the potential involvement of Hsp60 in Alzheimer’s disease (AD) and Type II Diabetes Mellitus (T2DM), which are known to share impaired key pathways and molecular dysfunctions. Fragmentary data reported in the literature reveal interesting links between the altered expression level or localization of this chaperonin and several disease conditions. The present work offers an overview of the past and more recent knowledge about Hsp60 and its role in the most important cellular processes to shed light on neuronal Hsp60 as a potential common target for both pathologies. The absence of any effective cure for AD patients makes the identification of a new molecular target a promising path by which to move forward in the development of new drugs and/or repositioning of therapies already used for T2DM.

Chaperones—A New Class of Potential Therapeutic Targets in Alzheimer’s Disease

“…Hsp60 increased [85] Inhibiting Aβ amyloid aggregation by closing molecular pathways leading to peptide fibrillogenesis [86] Hsp70 increased [85] Protecting neurons from intracellular accumulation of Aβ through promoting the clearance of Aβ [87] Hsp90 increased [42] Regulating tau phosphorylation [42] p23 decreased [88] Facilitating the adenosine triphosphate-driven cycle of Hsp90 binding to client proteins [88] PP5 decreased [89] Dephosphorylation of tau [89] STI1/Hop increased [90] Clearance of tau [91] Stg1 decreased [42] Clearance of tau [42] Table 2. Cont.…”