Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Str. 10, D-13125 Berlin, Germany.
Rev Neurosci. 2010;21(4):315-29. doi: 10.1515/revneuro.2010.21.4.315.
The proteolytic breakdown of the amyloid precursor protein (APP) to neurotoxic amyloid-beta peptides in the brain has been recognized as a major pathological pathway in Alzheimer's disease (AD). Yet, the factors that control the processing of APP and their potential contribution to the common sporadic form of AD remain poorly understood. Here, we review recent findings from studies in patients and in animal models that led to the identification of a unique sorting receptor for APP in neurons, designated SORLA/SORL1, that emerges as a key player in amyloidogenic processing and as major genetic risk factor for AD.
淀粉样前体蛋白(APP)在大脑中的蛋白水解断裂,产生神经毒性的淀粉样β肽,这已被认为是阿尔茨海默病(AD)的主要病理途径。然而,控制 APP 加工的因素及其对常见散发性 AD 的潜在贡献仍知之甚少。在这里,我们回顾了在患者和动物模型中的研究的最新发现,这些发现导致了神经元中 APP 的独特分选受体 SORLA/SORL1 的鉴定,该受体被认为是淀粉样生成处理的关键因素,也是 AD 的主要遗传风险因素。