阿尔茨海默病的淀粉样蛋白前体是神经生长因子对神经突生长作用的介质。

The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth.

作者信息

Milward E A, Papadopoulos R, Fuller S J, Moir R D, Small D, Beyreuther K, Masters C L

机构信息

Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Neuron. 1992 Jul;9(1):129-37. doi: 10.1016/0896-6273(92)90228-6.

DOI:10.1016/0896-6273(92)90228-6

PMID:1632967

Abstract

The beta A4 protein, the major component of the amyloid deposition characterizing Alzheimer's disease, derives from the amyloid protein precursor (APP), an integral membrane protein with soluble derivatives. The function of APP is unknown. Both soluble and membrane-associated human brain APP (10(-10) M) significantly increased (P less than 0.025) neurite length and branching in pheochromocytoma PC12 cells, but did not affect the number of neurites per cell. At higher concentrations, APP was cytotoxic, with a half-maximal concentration of 5 x 10(-9) M. Nerve growth factor (NGF) is known to affect APP expression in vivo and in vitro. Antibodies to APP specifically diminished the effects of NGF on neurite length and branching. Thus APP may act to mediate neurite outgrowth promotion by NGF.

摘要

β淀粉样蛋白A4是阿尔茨海默病特征性淀粉样沉积的主要成分，它来源于淀粉样前体蛋白（APP），一种具有可溶性衍生物的整合膜蛋白。APP的功能尚不清楚。可溶性和膜相关的人脑APP（10⁻¹⁰M）均显著增加（P<0.025）嗜铬细胞瘤PC12细胞的神经突长度和分支，但不影响每个细胞的神经突数量。在更高浓度下，APP具有细胞毒性，半数最大浓度为5×10⁻⁹M。已知神经生长因子（NGF）在体内和体外都会影响APP的表达。APP特异性抗体可特异性减弱NGF对神经突长度和分支的影响。因此，APP可能介导NGF促进神经突生长的作用。