The role of tau in Alzheimer’s Disease: Effects of Lys-280 and Lys-281 acetylation on tau function and structure Public Deposited

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Last Modified
  • March 20, 2019
Creator
  • Constance, Brian
    • Affiliation: School of Medicine, Department of Pharmacology
Abstract
  • The tau protein is implicated in Alzheimer’s disease (AD), and it is a prominent feature of AD pathology. In AD, tau's normal ability to stabilize microtubules (MTs) is impaired, and tau becomes aggregated. Aberrant post-translational modifications (PTMs) of tau may provide an explanation for why this occurs. There are mounting indications that tau acetylation plays a role in AD, with acetylated K280 being discovered as a marker of tau aggregation in AD brain. We hypothesize that acetylation of lysines in tau’s microtubule binding region (MTBR) causes a loss of tau stabilizing function and a gain of propensity to form aggregates. Using lysine to glutamine (K->Q) mutations to model acetylation, we provide evidence suggesting that single (K280) or double (K280/K281) acetylation inhibits MT assembly. Furthermore, we implicate the K280 acetylation in accelerating tau aggregation, and in the seeding of aberrantly phosphorylated, tau aggregation.
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Rights statement
  • In Copyright
Advisor
  • Cohen, Todd
  • Nicholas, Robert
  • Graves, Lee
Degree
  • Master of Science
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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