MOCA is a member of a new family of 'adaptor' proteins and binds to presenilin, a protein responsible for about 70% of the early onset familial AD cases. Previous data have shown that MOCA is lost in the soluble fraction of AD brains vs. the age-matched controls, is associated with neurofibrillary tangles, and decreases the secretion of amyloid precursor protein (APP) and the production of Abeta peptides. These data suggest that MOCA may play a major role in AD and in other brain functions. The proposed project will further study the function of the protein and the underlying mechanisms. First, the role of MOCA in regulating cell-cell adhesion, an important process that has been implicated in memory function, will be studied. The effects of MOCA on the expression, trafficking, localization, and phosphorylation of cell-cell adhesion components including N-cadherin and beta-catenin, will be examined. Second, the mechanism of the MOCA effect on APP secretion will be studied by testing the hypothesis that the proteasome is involved in its regulation. Third, the biological function of MOCA will be studied using in vivo animal models by generating MOCA null-mutant mice and Drosophila. The phenotypes of these animals will be scrutinized along with the physiological significance of the genetic change. The above studies will outline a basic framework for MOCA function in the normal brain and may lead to the discovery of a new direction for understanding AD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS045476-03
Application #
6930546
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Refolo, Lorenzo
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$51,116
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037