Department of Biochemistry, and Department of Cardiology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Chu Kochen Honors College, Zhejiang University, Hangzhou 310058, China.
Cells. 2021 Aug 30;10(9):2247. doi: 10.3390/cells10092247.
Stress granules are conserved cytosolic ribonucleoprotein (RNP) compartments that undergo dynamic assembly and disassembly by phase separation in response to stressful conditions. Gene mutations may lead to aberrant phase separation of stress granules eliciting irreversible protein aggregations. A selective autophagy pathway called aggrephagy may partially alleviate the cytotoxicity mediated by these protein aggregates. Cells must perceive when and where the stress granules are transformed into toxic protein aggregates to initiate autophagosomal engulfment for subsequent autolysosomal degradation, therefore, maintaining cellular homeostasis. Indeed, defective aggrephagy has been causally linked to various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this review, we discuss stress granules at the intersection of autophagy and ALS pathogenesis.
应激颗粒是保守的细胞质核糖核蛋白（RNP）区室，通过相分离在应激条件下动态组装和拆卸。基因突变可能导致应激颗粒的异常相分离，引发不可逆转的蛋白质聚集。一种称为聚集体自噬的选择性自噬途径可能部分缓解这些蛋白质聚集体介导的细胞毒性。细胞必须感知应激颗粒何时何地转化为有毒的蛋白质聚集体，以启动自噬体吞噬，随后进行自溶体降解，从而维持细胞内稳态。事实上，聚集体自噬功能缺陷与各种神经退行性疾病有关，包括肌萎缩侧索硬化症（ALS）。在这篇综述中，我们讨论了自噬和 ALS 发病机制中应激颗粒的作用。
