Ling Yan, Morgan Kevin, Kalsheker Noor
Division of Clinical Chemistry, Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Int J Biochem Cell Biol. 2003 Nov;35(11):1505-35. doi: 10.1016/s1357-2725(03)00133-x.
The processing of amyloid precursor protein (APP) generates amyloid-beta (Abeta) peptides 1-40 and 1-42. The latter is neurotoxic and its accumulation results in amyloid fibril formation and the generation of senile plaques, the hallmark of Alzheimer's disease (AD). Whilst there has been considerable progress made in understanding the generation of Abeta by alpha-, beta- and gamma-secretase activity on APP, recently enzymes involved in the degradation of Abeta have been identified including neprilysin and insulin-degrading enzyme (IDE). We review the pathways involved in proteolytic processing of APP and discuss the potential implications of aberrant proteolysis on neurodegeneration. It is conceivable that single nucleotide polymorphisms (SNPs) in the regulatory regions of genes in these proteolytic cascades, which alter their expression, could contribute to some of the age-related changes seen in AD.
淀粉样前体蛋白（APP）的加工过程会产生β淀粉样蛋白（Aβ）1-40和1-42肽段。后者具有神经毒性，其积累会导致淀粉样纤维形成和老年斑的产生，而老年斑是阿尔茨海默病（AD）的标志。虽然在理解α-、β-和γ-分泌酶对APP的作用从而产生Aβ方面已经取得了相当大的进展，但最近已鉴定出参与Aβ降解的酶，包括中性内肽酶和胰岛素降解酶（IDE）。我们综述了APP蛋白水解加工所涉及的途径，并讨论了异常蛋白水解对神经退行性变的潜在影响。可以想象，这些蛋白水解级联反应中基因调控区域的单核苷酸多态性（SNP）会改变其表达，这可能是AD中一些与年龄相关变化的原因。
