Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
J Neurosci Res. 2023 Oct;101(10):1611-1623. doi: 10.1002/jnr.25225. Epub 2023 Jun 19.
There are many cellular mechanisms implicated in the initiation and progression of neurodegenerative disorders. However, age and the accumulation of unwanted cellular products are a common theme underlying many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Niemann-Pick type C. Autophagy has been studied extensively in these diseases and various genetic risk factors have implicated disruption in autophagy homoeostasis as a major pathogenic mechanism. Autophagy is essential in the maintenance of neuronal homeostasis, as their postmitotic nature makes them particularly susceptible to the damage caused by accumulation of defective or misfolded proteins, disease-prone aggregates, and damaged organelles. Recently, autophagy of the endoplasmic reticulum (ER-phagy) has been identified as a novel cellular mechanism for regulating ER morphology and response to cellular stress. As neurodegenerative diseases are generally precipitated by cellular stressors such as protein accumulation and environmental toxin exposure the role of ER-phagy has begun to be investigated. In this review we discuss the current research in ER-phagy and its involvement in neurodegenerative diseases.
有许多细胞机制参与神经退行性疾病的发生和进展。然而，年龄的增长和不需要的细胞产物的积累是许多神经退行性疾病（包括阿尔茨海默病、帕金森病和尼曼-匹克 C 型）的共同主题。自噬在这些疾病中得到了广泛的研究，各种遗传风险因素表明，自噬动态平衡的破坏是主要的致病机制。自噬对于维持神经元的内稳态至关重要，因为它们的有丝分裂后特性使它们特别容易受到积累的有缺陷或错误折叠的蛋白质、易患病的聚集物和受损细胞器的损害。最近，内质网的自噬（ER-phagy）已被确定为一种新的细胞机制，用于调节内质网的形态和对细胞应激的反应。由于神经退行性疾病通常是由细胞应激引起的，如蛋白质积累和环境毒素暴露，因此 ER-phagy 的作用开始被研究。在这篇综述中，我们讨论了 ER-phagy 的当前研究及其在神经退行性疾病中的作用。
