Funderburk Sarah F, Marcellino Bridget K, Yue Zhenyu
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
Mt Sinai J Med. 2010 Jan-Feb;77(1):59-68. doi: 10.1002/msj.20161.
The autophagy pathway is the major degradation pathway of the cell for long-lived proteins and organelles. Dysfunction of autophagy has been linked to several neurodegenerative disorders that are associated with an accumulation of misfolded protein aggregates. Alzheimer's disease, the most common neurodegenerative disorder, is characterized by 2 aggregate forms, tau tangles and amyloid-beta plaques. Autophagy has been linked to Alzheimer's disease pathogenesis through its merger with the endosomal-lysosomal system, which has been shown to play a role in the formation of the latter amyloid-beta plaques. However, the precise role of autophagy in Alzheimer's disease pathogenesis is still under contention. One hypothesis is that aberrant autophagy induction results in an accumulation of autophagic vacuoles containing amyloid-beta and the components necessary for its generation, whereas other evidence points to impaired autophagic clearance or even an overall reduction in autophagic activity playing a role in Alzheimer's disease pathogenesis. In this review, we discuss the current evidence linking autophagy to Alzheimer's disease as well as the uncertainty over the exact role and level of autophagic regulation in the pathogenic mechanism of Alzheimer's disease.
自噬途径是细胞对长寿蛋白和细胞器的主要降解途径。自噬功能障碍与几种神经退行性疾病有关，这些疾病与错误折叠的蛋白质聚集体的积累有关。阿尔茨海默病是最常见的神经退行性疾病，其特征是两种聚集形式，即tau缠结和β淀粉样蛋白斑块。自噬通过与内体-溶酶体系统结合而与阿尔茨海默病发病机制相关联，内体-溶酶体系统已被证明在后者β淀粉样蛋白斑块的形成中起作用。然而，自噬在阿尔茨海默病发病机制中的确切作用仍存在争议。一种假设是异常的自噬诱导导致含有β淀粉样蛋白及其生成所需成分的自噬泡积累，而其他证据则表明自噬清除受损，甚至自噬活性的整体降低在阿尔茨海默病发病机制中起作用。在这篇综述中，我们讨论了将自噬与阿尔茨海默病联系起来的当前证据，以及在阿尔茨海默病致病机制中自噬调节的确切作用和水平的不确定性。
