Heat shock proteins regulates Tau protein aggregation in Alzheimer's disease.

Alzheimer's disease is one of the neurodegenerative diseases characterized by loss of integrity and function of the cell, leading to progressive neuronal loss and ultimately dementia. Tau is one of the most soluble protein mainly involved in assembly and disassembly of microtubules (MT) which helps in the anterograde and retrograde transport of cargos. However in AD conditions Tau is subjected to various insults such as hyperphosphorylation, glycation, glycosylation, truncation, acetylation, oxidation etc., which leads to the loss-of-function. Thus modified Tau loses its affinity for MT and aggregates to form toxic oligomers followed by matured neurofibrillary tangles (NFTs) which attains cross-β structure. The cellular machinery such as chaperones, ubiquitin-proteasome system (UPS) and lysosomes tries to resolve these aggregates and helps in its clearance. During AD pathology the cellular machinery fails to clear aggregates and leads to neuronal death. In this aspect several strategies have been employed to prevent Tau aggregation that includes inhibitors for kinases, activators for phosphatases, small molecule activators of heat shock protein response and small molecules that can prevent Tau aggregation and increases its association with chaperones.