Effects of Tau Phosphorylation upon Microtubule Binding and Regulation of Dynamics; Implications for Alzheimer’s and Related Dementias

Tau is a microtubule-associated protein that regulates microtubule behavior, which is in turn critical for proper maintenance and development of the central nervous system. On the other hand, abnormal tau action is associated with more than 20 different neural disorders, including Alzheimer's disease, an age-related and irreversible neurodegenerative disorder. An abundance of biochemical and genetic data implicates abnormal tau hyperphosphorylation as a causative factor in tau dysfunction . Our project aims t o assess the effects of these pathological tau phosphorylation events on the ability of tau to performs its normal functions, including microtubule binding, microtubule assembly, and the regulation of microtubule dynamics. Historically, research on this subject has targeted only single phosphorylation events. This project aims to methodically study both single and the more biologically relevant combinatorial phosphorylation patterns in order to assess the effects of tau phospohorylation in a more in vivo-like context.