《生命科学》 2008, 20(2):

Beta-淀粉样蛋白前体蛋白胞内结构域(AICD)研究进展

张 弦，许华曦*，张云武*

(厦门大学生物医学研究院，厦门大学生命科学学院分子细胞神经科学实验室, 厦门361005)

摘　要：摘　要：老年性痴呆症(Alzheimer抯 disease, AD)一个重要的病理学特征，是在神经细胞外形成由b-淀粉样蛋白(b-amyloid, Ab)组成的淀粉样斑(amyloid plaques)。b-淀粉样蛋白前体蛋白(b-amyloid procursor protein，APP)经b-分泌酶和g-分泌酶依次水解后产生Ab和APP胞内结构域(APP intracellular domain，AICD)。现在已经知道Ab在AD的发病机制中起着关键作用，但是关于AICD的生理及病理功能还不清楚。近年来研究发现AICD可以与细胞内多种蛋白相互作用，而且AICD在基因转录、细胞凋亡以及APP的加工和运输过程中均有调节功能。本文针对这一领域的研究进展，对AICD的生理及病理功能进行探讨。
关键词：老年性痴呆症; b-淀粉样蛋白前体蛋白; APP胞内结构域
中图分类号：R749.1; Q51　　文献标识码：A

Advances in understanding the beta-amyloid precursor protein intracellular domain

ZHANG Xian, XU Hua-xi*, ZHANG Yun-wu*

(Institute for Biomedical Research and Laboratory of Molecular and Cellular Neuroscience, School of Life Sciences, Xiamen University, Xiamen 361005, China)

Abstract: Abstract: One of the neuropathologic hallmarks of Alzheimer’s disease (AD) is the presence of senile plaques which consist of b-amyloid peptide (Ab) in the brain. Ab is derived from b-amyloid precursor protein (APP) through sequential cleavages by the b-secretase and the g-secretase. In addition to Ab, g-cleavage releases the intracellular domain of APP (AICD). However, although it is well-established that Ab is the prime culprit for AD pathogenesis, the physio/pathological functions of AICD remain largely elusive. Here we review recent progress toward elucidating the functional roles of AICD, which include modulating intracellular trafficking/processing of APP, inducing apoptosis, and regulating gene expression at transcriptional level.
Key words: Alzheimer‘s disease; b-amyloid precursor protein; b-amyloid precursor protein intracellular domain