Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Int J Mol Sci. 2021 Mar 24;22(7):3330. doi: 10.3390/ijms22073330.
Alzheimer's disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including amyloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.
阿尔茨海默病（AD）是一种使人衰弱的神经退行性疾病，目前尚无治愈方法。在 AD 患者的大脑中已经描述了几种病理改变，但 AD 的最终致病机制仍难以捉摸。AD 的经典标志物，包括淀粉样斑块（Aβ）和tau 缠结（tau），是 AD 最受研究的特征。不幸的是，迄今为止，针对这些病理的所有努力都未能在 AD 患者中显示出预期的疗效。神经炎症和自噬受损是 AD 的另外两个主要已知病理。据报道，这些病理在 AD 大脑中很早就存在，早在出现任何 AD 临床症状之前就已经存在。小胶质细胞是大脑中的主要炎症细胞，许多研究人员认为它们是在 AD 中找到可行的治疗靶点的下一个希望。有趣的是，AD 中这些细胞的自噬和线粒体自噬似乎也发生了变化。在细胞内，自噬和炎症以双向方式相互作用。在本综述中，我们简要讨论了 AD 中的自噬和线粒体自噬概述，然后全面讨论了这些途径在小胶质细胞中的作用及其在 AD 发病机制中的参与。
