Istituto di Cristallografia - CNR

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

: 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.

International journal of molecular sciences (Online)
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Stefania Zimbone, Maria Carmela Di Rosa, Santina Chiechio and Maria Laura Giuffrida