Alzheimer's disease ranks the first cause for senile dementia. The amyloid cascade is proposed to contribute to the pathogenesis of this disease. In this cascade, amyloid β peptide (Aβ) is produced through a sequential cleavage of amyloid precursor protein (APP) by β and γ secretases, while its cleavage by α secretase precludes Aβ production and generates neurotrophic sAPPα. Thus, enhancing α secretase activity or suppressing β and γ cleavage may reduce Aβ formation and ameliorate the pathological process of the disease. Several regulatory mechanisms of APP cleavage have been established. The present review mainly summarizes the signaling pathways pertinent to the regulation of APP β cleavage.
阿尔茨海默病是造成老年人痴呆的首要因素。 淀粉样蛋白级联假说认为淀粉样蛋白是阿尔茨海默病的致病因子, 其在大脑中的含量高低对疾病的发生有重要意义。 β淀粉样蛋白由淀粉样前体蛋白相继经 β 和γ分泌酶切割产生, 而α分泌酶的切割既排除了β淀粉样蛋白的形成, 又能产生具有神经保护作用的片段。 因此, 抑制β或γ切割, 或者增强α切割, 都可以减少β淀粉样蛋白的积累, 改善阿尔茨海默病的病理表现。 淀粉样前体蛋白切割的调控机理, 目前已被广泛研究。 本文就淀粉样前体蛋白β切割的调控机理作一综述。