Notch Signaling as a Model to Deteremine the Function of PS1

Alison Goate, DPhil
Washington University (St. Louis, MO)
Year Awarded:
1999
Grant Duration:
April 1, 1999 to March 31, 2001
Disease:
Alzheimer's Disease
Award Amount:
$199,556
Grant Reference ID:
A1999065
Award Type:
Standard
Award Region:
US Midwestern
Alison Goate, DPhil

Notch Signaling as a Model to Deteremine the Function of PS1

Details


Mutations in the gene presenilin 1 (PS1) can cause Alzheimer's disease and result in increased levels of Ab42, a form of APP that causes amyloid plaques. Other data have suggested that PS1 is required for normal APP processing, but the precise function of PS1 in APP processing is unknown. PS1 also appears to be necessary for signaling through the Notch pathway. The Notch pathway begins on the surface of cells, and turning it on is important during embryonic development. The interaction of Notch with PS1 is easier to study than the interaction of PS1 with APP, and Dr. Goate is taking advantage of this fact to better understand the function of PS1. Using the information gained from studying PS1-Notch interactions, she will then be able to ask more informed questions about PS1-APP interactions, and how these interactions are altered in Alzheimer's disease.

Publications

Nowotny, P., Gorski, S., Han, S. W., Philips, K., Ray, W., Nowotny, V., Jones, C., Clark, R., Cagan, R., and Goate, A. (2000) Posttranslational Modification and Plasma Membrane Localization of the Drosophila Melanogaster Presenilin. Molecular and Cellular Neuroscience. 15:88-89.  

Ray, W.J., Yao, M., Nowotny, P., Mumm, J., Zhang, W., Wu, J.Y., Kopan, R., and Goate, A.M. (1999) Evidence for a physical interaction between presenilin, and Notch. Proc. Natl. Acad. Sci, USA. 96:3263-3268.  

Ray, W.J., Yao, M., Mumm, J., Schroeter, E., Saftig, P., Wolfe, M., Selkoe, D., Kopan, R., Goate, A. (1999) Cell surface presenilin-1 participates in the y-secretase-like proteolysis of notch. Journal of Biological Chemistry. 274: 36801-36807.  

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