The long term goal of this work is to elucidate the underlying molecular mechanisms leading to the development of neurofibrillary tangles(NFTs), a hallmark pathological feature of Alzheimer's disease.We will focus on the microtubule associated protein, tau, known to be the major molecular component of NFTs. Whereas normal tau is capable of interacting directly with microtubules and regulating their dynamics and stability, the abnormal tau found in NFTs is unable to bind microtubules concomitant with altered structural and functional properties. This project is designed to identify critical domains of tau and tubulin involved in the tau-tubulin interaction and possibly tau-tau interaction using the yeast two-hybrid system and a covalent cross- linking biochemical assay. The information obtained in these two assays will be used to perform X-ray crystallography studies of tau and tau-tubulin co-crystals (a join effort of the Feinstein and Kohlstaedt labs) by delimiting the important domains involved in the interactions. Understanding normal tau action provides an important foundation for the study of abnormal tau action in NFTs, a critical prerequisite for the development of rational therapies to address the problem of NFT formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS010212-02
Application #
2460480
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Oliver, Eugene J
Project Start
1997-08-01
Project End
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Santa Barbara
Department
Type
Organized Research Units
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106