Tau proteotasis in Alzheimer's disease.

Abstract

Tau protein accumulation is one of the characteristic features of Alzheimer's disease (AD). Their accumulation is driven by the formation of intermediate toxic oligomers of Tau to the highly ordered neurofibrillary tangles. Cellular machineries engage different types of proteins such as, chaperone-co-chaperones complex, ubiquitin, kinases, proteases etc., to clear the aberrantly accumulated Tau protein which otherwise would cause neuronal death. In the milieu of proteotoxicity, it would be significant for the cell to follow a specific path for Tau clearance. Under this circumstance, cells express key proteins and other accessory proteins specific to the pathway. This is known to be dependent on the post-translational modifications and mutations associated with Tau. The processes involved maintenance of proteins homeostasis in cells collectively called proteostasis. The proteostasis involve the synthesis of proteins by ribosomes, protein folding mostly by chaperons and the degradation of improperly folded or unwanted proteins. Autophagy is the mechanism to eradicate unwanted, non-functional and toxic proteins from the cell. Proteostasis plays a pivotal role in maintaining the normal cellular environment in the expense of considerable amount of energy. AD is the prevalent type of dementia associated with aging, which is characterized by aggregation of Tau.