Tau protein and Alzheimers disease / 中国药理学通报

ABSTRACT

Tau is a multifunctional protein that are originally identified as a microtubule-associated protein. Tau is mainly expressed in neurons. There is a protein phosphorylation/dephosphorylation imbalance and tau is abnormally hyperphosphorylatied in the brain of patients with AD and in this form it is the major protein subunit of paired helical filaments/neurofibrillary tangles(PHF/NFT). The modulation of the activities of phosphatase(PP)-2A, PP1 and tau kinase, such as GSK-3, cdk5 and MAPK effect tau protein hyperphosphorylation. It is unclear about the relation between tau and A? in AD, increased or altered A? production may be an initiating event in the pathogenic process in AD; but aberrant alternations in tau function are likely necessary for the subsequent neuronal dysfunction and death. Therefore, clearly defining the metabolism and function of tau in both normal and disease states is necessary for our understanding of AD and the development of appropriate therapeutic interventions.