Delineating Pathogenic Interactions of LRRK2 and Tau at the Microtubule
Abstract
Lay Abstract: Over a million Americans suffer from Parkinson disease (PD), a devastating illness triggered by the loss of a specific group of neurons in the brain. PD robs patients of their ability to walk, work, and care for themselves, ultimately causing death. Despite an enormous need, there is not a single medication that stops or even slows PD. My research focuses on the most common cause of inherited PD, mutations (abnormalities) in a poorly understood gene called LRRK2. Even when no family member has PD, mutations in LRRK2 can influence a person s risk of getting PD. Therefore, it is very important to understand what LRRK2 does in the cell and how LRRK2 mutations change its function. There is some evidence that LRRK2 functions at a certain location in the cell called the microtubule and that mutant LRRK2 at the microtubule may play a critical role in causing PD. Recently, I found a new protein whose function seems to be to bring LRRK2 microtubule where it puts a tag on LRRK2, marking it for destruction. This is exciting because another protein that causes death of neurons, tau, is also found at the microtubule. LRRK2 and tau can interact in a test tube, and in certain people with PD, abnormal tau is found in their brains. Understanding how and why LRRK2 and tau interact is the focus of this grant. I propose to study LRRK2 and tau in more detail: First, by examining if LRRK2 and tau interact at the microtubule and, if so, to determine the outcomes of this interaction. Second, by finding if there are other proteins that interact with LRRK2 and tau at the microtubule and identifying them, and, finally, by evaluating whether tau can be tagged for destruction in the same way LRRK2 can. All of these aims attempt to determine how LRRK2 causes PD, with the ultimate goal of this work to discover novel proteins and pathways that will serve as future drug targets. My father has PD. I have been determined to be a researcher studying diseases like PD since my freshman year of college, well before my father was diagnosed with the disease; however, my father s diagnosis only made me more determined to advance this field. Because of this, I decided to become a research physician and run a laboratory dedicated to understanding and treating PD. As a recently trained neuropathologist with a strong background in cell and molecular biology, I believe I am in a unique position to make key discoveries that aid patients with PD. The proposed research plan will allow me to develop into an independent researcher poised to make these discoveries.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810376
Entities
People
- Anne Hiniker
Organizations
- United States Army
- University of California, San Francisco