Updates on Aß Processing by Hsp90, BRICHOS, and Newly Reported Distinctive Chaperones.

ABSTRACT

Alzheimer's disease (AD) is an extremely devastating neurodegenerative disease, and there is no cure for it. AD is specified as the misfolding and aggregation of amyloid-ß protein (Aß) and abnormalities in hyperphosphorylated tau protein. Current approaches to treat Alzheimer's disease have had some success in slowing down the disease's progression. However, attempts to find a cure have been largely unsuccessful, most likely due to the complexity associated with AD pathogenesis. Hence, a shift in focus to better understand the molecular mechanism of Aß processing and to consider alternative options such as chaperone proteins seems promising. Chaperone proteins act as molecular caretakers to facilitate cellular homeostasis under standard conditions. Chaperone proteins like heat shock proteins (Hsps) serve a pivotal role in correctly folding amyloid peptides, inhibiting mitochondrial dysfunction, and peptide aggregation. For instance, Hsp90 plays a significant role in maintaining cellular homeostasis through its protein folding mechanisms. In this review, we analyze the most recent studies from 2020 to 2023 and provide updates on Aß regulation by Hsp90, BRICHOS domain chaperone, and distinctive newly reported chaperones.