Sabo S L, Lanier L M, Ikin A F, Khorkova O, Sahasrabudhe S, Greengard P, Buxbaum J D
Laboratory of Molecular and Cellular Neuroscience and Zachary and Elizabeth M. Fisher Center, The Rockefeller University, New York, New York 10021, USA.
J Biol Chem. 1999 Mar 19;274(12):7952-7. doi: 10.1074/jbc.274.12.7952.
The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.
阿尔茨海默病淀粉样斑块的主要成分β淀粉样蛋白（Aβ）来源于阿尔茨海默病淀粉样蛋白前体（APP）的蛋白水解加工。FE65是一种在脑中高表达的与APP结合的蛋白。尽管多个实验室已在体外对APP-FE65相互作用进行了表征，但这种相互作用与阿尔茨海默病的潜在相关性仍不明确。我们在此证明，APP和FE65共定位于内质网/高尔基体，也可能定位于内体。此外，FE65增加APP向细胞表面的转运以及α分泌酶切割的APP（αAPPs）和Aβ的分泌。Aβ分泌显著（4倍）依赖于FE65，这表明抑制FE65与APP相互作用的药物可能会减少脑中Aβ的分泌，因此可能有助于预防或减缓淀粉样斑块的形成。
