ABSTRACT:
Alzheimer’s disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aβ) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response. In AD, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70. Therefore, we review here to further discuss the recent advances and challenges in targeting Hsp90 for AD therapy.Heat shock proteins (HSP) are a group of proteins that impressed by heat shock, the subgroup of these proteins are related proteins functionally take part in the folding and unfolding of other proteins. Their expression is increased in high temperatures or other stress that cells are exposed. The upregulation of the heat shock proteins is important to the heat shock response and is induced by heat shock factor (HSF). Heat shock proteins are named by their molecular weight. For example, HSP60 has 60 kilodaltons (kd) molecular weight