Menéndez-González M, Pérez-Pinera P, Martínez-Rivera M, Calatayud M T, Blázquez Menes B
Neurology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
Neurodegener Dis. 2005;2(6):277-83. doi: 10.1159/000092315.
Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor (KPI) domain. KPI is one of the main serine protease inhibitors. Protein and mRNA KPI(+)APP levels are elevated in Alzheimer's disease (AD) brain and are associated with increased amyloid beta deposition. In the last years increasing evidence on multiple points in the amyloid cascade where KPI(+)APP is involved has been accumulated, admitting an outstanding position in the pathogenesis of AD to the KPI domain. This review focuses on the APP processing, the molecular activity of KPI and its physiological and pathological roles and the KPI involvement in the amyloid cascade through the nerve growth factor, the lipoprotein receptor-related protein, the tumor necrosis factor-alpha converting enzyme and the Notch1 protein.
淀粉样前体蛋白（APP）的可变剪接可产生含有库尼茨蛋白酶抑制剂（KPI）结构域的APP异构体。KPI是主要的丝氨酸蛋白酶抑制剂之一。在阿尔茨海默病（AD）大脑中，蛋白质和mRNA水平的KPI（+）APP升高，且与淀粉样β沉积增加有关。近年来，关于KPI（+）APP参与淀粉样蛋白级联反应多个环节的证据不断积累，这使得KPI结构域在AD发病机制中占据突出地位。本综述聚焦于APP加工过程、KPI的分子活性及其生理和病理作用，以及KPI通过神经生长因子、脂蛋白受体相关蛋白、肿瘤坏死因子-α转换酶和Notch1蛋白参与淀粉样蛋白级联反应的情况。
