专利号:US-6333317-B1 优先权日:1997-03-28 标 题:Regulation of amyloid precursor protein (APP) expression by administration of an estrogenic compound 发明人:LEE ROBERT K K; WURTMAN RICHARD J 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:It has been discovered that lipophilic hormones that interact with cytosolic or nuclear receptors regulate APP expression and synthesis, through modification of APP mRNA stability and/or regulation of APP gene transcription and translation activities. These studies demonstrate that the treatment of brain cells with estrone or 17β-estradiol results in a reduction in the level of APP holoprotein expression, without a concomitant change in the total level of cell protein. The reduction in the level of APP holoprotein caused by estrone or 17β-estradiol is also expected to reduce the production of neurotoxic APP fragments. In as much as estrogen deficiency in postmenopausal women is associated with a higher incidence of Alzheimer's disease, this discovery opens the possibility that estrogen therapy may prevent some of the neurodegenerative and cognitive changes associated with Alzheimer's disease, aging and other disease conditions associated with such neurodegenerative and cognitive decline.