Function and regulation of cis P ‐tau in the pathogenesis and treatment of conventional and nonconventional tauopathies

Cis –trans isomerization of protein plays an important role in protein folding, function, and degradation, which is regulated by peptidyl-proline isomerases (PPIases). The cis P-tau but not trans P-tau is resistant to protein dephosphorylation and degradation and also prone to protein aggregation and serves as an early driver of multiple neurodegenerative disease including Alzheimer disease (AD), traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), and vascular contributions to cognitive impairment and dementia (VCID). Cis P-tau antibody is the only clinical-stage therapeutic fo r AD that has shown the efficacy in animal models of not only AD but also TBI and stroke, which are very early stages of dementia. In this article, we review the role of cis P-tau in neurodegenerative diseases and its regulation as a potential drug target. A schematic drawing of cis and trans pT231P of tau protein. Cis but not trans P-tau is induced by multiple stresses and contributes to neurodegenerative diseases. Cis P-tau is converted into trans P-tau by Pin1. AbstractConventional tauopathies are a group of disease characterized by tau inclusions in the brains, including Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and certain types of frontotemporal dementia (FTD), among which AD is the most prevalent. Extensive post-translational modifications, especially hyperphosphorylation, and abnormal aggregation of...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research