Li Yan-Yan, Qin Zheng-Hong, Sheng Rui
Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences of Soochow University, Suzhou, 215123, China.
Neurosci Bull. 2024 Mar;40(3):363-382. doi: 10.1007/s12264-023-01120-y. Epub 2023 Oct 19.
Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia. Autophagy maintains cell homeostasis in the nervous system via degradation of misfolded proteins, elimination of damaged organelles, and regulation of apoptosis and inflammation. AMPK-mTOR, Beclin 1, TP53, endoplasmic reticulum stress, and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological diseases. Here, we discuss the role, functions, and signal pathways of autophagy in neurological diseases, which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.
自噬涉及将细胞质物质隔离并运输到溶酶体,在溶酶体中蛋白质、脂质和细胞器被降解并循环利用。根据细胞质成分的吞噬方式,自噬可分为巨自噬、微自噬和分子伴侣介导的自噬。最近,许多研究发现自噬在神经疾病中起重要作用,包括阿尔茨海默病、帕金森病、亨廷顿病、神经元兴奋性毒性和脑缺血。自噬通过降解错误折叠的蛋白质、清除受损细胞器以及调节细胞凋亡和炎症来维持神经系统中的细胞稳态。AMPK-mTOR、Beclin 1、TP53、内质网应激等信号通路参与自噬的调节,并可作为神经疾病的潜在治疗靶点。在此,我们讨论自噬在神经疾病中的作用、功能和信号通路,这将有助于揭示神经疾病的致病机制并为治疗提供新的靶点。