Abstract
Tau is a brain microtubule-associated protein that regulates microtubule structure and function. Prominent tau neurofibrillary pathology is a common feature in a number of neurodegenerative disorders collectively referred to as tauopathies, the most common of which is Alzheimer’s disease. Regulation of tau behavior and function under physiological and pathological conditions is mainly achieved through posttranslational modifications, especially phosphorylation. Abnormal hyperphosphorylation of tau protein leads to its detachment from microtubules and promotes its self-assembly into toxic oligomers and paired helical filaments. The strong correlation that exists between phosphorylation and tau pathology has laid the foundation to look for tau kinase inhibitors as potential therapeutics. This chapter focuses on emerging therapeutic strategies aimed at reducing toxic phosphorylated tau levels through the inhibition of tau kinases.
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