Estrogen and Presenilin 1 in BAPP Trafficking and AB Generation

Huaxi Xu, PhD
Sanford-Burnham Medical Research Institute' (La Jolla, CA)
Year Awarded:
1999
Grant Duration:
April 1, 1999 to March 31, 2001
Disease:
Alzheimer's Disease
Award Amount:
$196,654
Grant Reference ID:
A1999066
Award Type:
Standard
Award Region:
US Northeastern
Huaxi Xu, PhD

Estrogen and Presenilin 1 in BAPP Trafficking and AB Generation

Details


Postmenopausal women who take estrogen as part of a long-term program of estrogen replacement are less likely to get Alzheimer's disease, or more likely to get it at an older age. Dr. Xu and coworkers were the first to show that estrogen may actually prevent or delay Alzheimer's by slowing the secretion of amyloid from neurons. Dr. Xu is working toward an understanding of how estrogen inhibits the production of toxic amyloid. By using techniques similar to the proposed studies on estrogen, Dr. Xu is also studying how presenilin affects the precursor protein, from which amyloid is derived. It is hoped that a better understanding of the mechanism behind amyloid secretion will lead to interventions to prevent, slow, or reverse the disease.

Publications

Gasparini, L., Gouras, G.K., Wang, R., Gross, R.S., Beal, M.F., Greengard, P., and Xu, H. (2001) Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. Journal of Neuroscience. 21(8):2561-2570. [Alzforum Recommended Paper]  

Gouras, G.K., Xu, H., Gross, R.S., Greenfield, J.P., Hai, B., Wang, R., Greengard, P. (2000) Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Proc Natl Acad Sci USA. 97(3):1202-1205. [Alzforum Recommended Paper]  

Gouras, G.K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J., Haroutunian, V., Buxbaum, J., Xu, H., Greengard, P., and Relkin, N. (2000) Intraneuronal Abeta42 accumulation in human brain. Am Journal of Pathology. 156(1):15-20 [Alzforum Recommended Paper][Alzforum Milestone Paper]  

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