The role of tau in Alzheimer’s Disease: Effects of Lys-280 and Lys-281 acetylation on tau function and structure Public Deposited
- Last Modified
- March 20, 2019
- Creator
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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.
- Date of publication
- August 2016
- Keyword
- DOI
- Resource type
- 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
- Language
- Parents:
This work has no parents.
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