State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Department of Pharmacy, Qilu Hospital, Shandong University, Qingdao, 266000, Shandong, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Toxicol Lett. 2020 May 15;324:20-29. doi: 10.1016/j.toxlet.2020.01.019. Epub 2020 Jan 24.
Similar to other types of neuronal degeneration, Parkinson's disease (PD) is characterized by the aggregation of a pathological protein, α-synuclein. The endoplasmic reticulum (ER) is the principal site of protein synthesis, quality control and degradation. Genetic mutants, environmental insults and other factors disturb ER balance and induce the accumulation of misfolded/unfolded proteins, which initiate ER stress and disturb normal cell function. ER stress perturbs Ca homeostasis and initiates the activation of autophagy and inflammasomes, which have been identified as risk factors for the development of PD. However, the mechanisms by which ER stress contributes to the processed of PD pathogenesis and development remain unclear. This review summarizes current knowledge of ER stress and highlights the principal role of ER stress in PD pathogenesis which may help reveal novel sight to illustrate the pathomechanism of PD.
与其他类型的神经元变性一样，帕金森病（PD）的特征是病理性蛋白α-突触核蛋白的聚集。内质网（ER）是蛋白质合成、质量控制和降解的主要场所。遗传突变、环境损伤和其他因素扰乱 ER 平衡并诱导错误折叠/未折叠蛋白质的积累，从而引发 ER 应激并扰乱正常细胞功能。ER 应激破坏 Ca 稳态并启动自噬和炎性小体的激活，这些已被确定为 PD 发展的危险因素。然而，ER 应激导致 PD 发病机制和发展的过程的机制仍不清楚。本综述总结了 ER 应激的最新知识，并强调了 ER 应激在 PD 发病机制中的主要作用，这可能有助于揭示新的视角来阐明 PD 的发病机制。
