老年性痴呆症(Alzheimer's disease,AD)一个重要的病理学特征,是在神经细胞外形成由β-淀粉样蛋白(β-amyloid,Aβ)组成的淀粉样斑(amyloid plaques)。β-淀粉样蛋白前体蛋白(β-amyloid procursor protein,APP)经β-分泌酶和γ-分泌酶依次水解后产生Aβ和APP胞内结构域(APP intracellular domain,AICD)。现在已经知道Aβ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。One of the neuropathologic hallmarks of Alzheimer’s disease (AD) is the presence of senile plaques which consist of β-amyloid peptide (Aβ) in the brain. Aβ is derived from β-amyloid precursor protein (APP) through sequential cleavages by the β-secretase and the γ-secretase. In addition to Aβ, γ-cleavage releases the intracellular domain of APP (AICD). However, although it is well-established that Aβ 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.国家自然科学基金(30672198);; 福建省高等学校新世纪优秀人才支持计
