Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Adv Exp Med Biol. 2018;1112:177-183. doi: 10.1007/978-981-13-3065-0_13.
The "amyloidogenic" proteolytic processing of the cell surface amyloid precursor protein (APP) produces amyloid-β, which causes a range of detrimental effects in the neuron, such as synaptic loss, and plays a key role in Alzheimer's disease. In contrast, "non-amyloidogenic" proteolytic processing, which involves the cleavage of APP by α-secretase, produces soluble amyloid precursor protein α (sAPPα) and is the most predominant proteolytic processing of APP in the healthy brain. Current research suggests that sAPPα plays a role in synaptic growth and plasticity, but whether this role is protective or detrimental is age-dependent. This review looks at the effects of increasing sAPPα during three time-points in life (in development, young adult, ageing/neurodegeneration) when synaptic plasticity plays an important role.
细胞表面淀粉样前体蛋白（APP）的“淀粉样生成”蛋白水解加工产生淀粉样β，它会对神经元造成一系列有害影响，如突触损失，并在阿尔茨海默病中发挥关键作用。相比之下，“非淀粉样生成”蛋白水解加工涉及 APP 被 α-分泌酶切割，产生可溶性淀粉样前体蛋白α（sAPPα），是健康大脑中 APP 最主要的蛋白水解加工方式。目前的研究表明，sAPPα 在突触生长和可塑性中发挥作用，但这种作用是保护还是有害取决于年龄。本综述着眼于在突触可塑性发挥重要作用的生命三个时间点（发育、年轻成年、衰老/神经退行性变）增加 sAPPα 的影响。
