Jeon Pureum, Lee Jin A
Department of Biotechnology and Biological Sciences, Hannam University, Daejeon, South Korea.
Front Cell Dev Biol. 2021 Feb 25;9:609698. doi: 10.3389/fcell.2021.609698. eCollection 2021.
Stress granules (SGs) are membraneless cytosolic granules containing dense aggregations of RNA-binding proteins and RNAs. They appear in the cytosol under stress conditions and inhibit the initiation of mRNA translation. SGs are dynamically assembled under stressful conditions and rapidly disassembled after stress removal. They are heterogeneous in their RNA and protein content and are cell type- and stress-specific. In post-mitotic neurons, which do not divide, the dynamics of neuronal SGs are tightly regulated, implying that their dysregulation leads to neurodegeneration. Mutations in RNA-binding proteins are associated with SGs. SG components accumulate in cytosolic inclusions in many neurodegenerative diseases, such as frontotemporal dementia and amyotrophic lateral sclerosis. Although SGs primarily mediate a pro-survival adaptive response to cellular stress, abnormal persistent SGs might develop into aggregates and link to the pathogenesis of diseases. In this review, we present recent advances in the study of neuronal SGs in physiology and pathology, and discuss potential therapeutic approaches to remove abnormal, persistent SGs associated with neurodegeneration.
应激颗粒（SGs）是无膜的胞质颗粒，含有RNA结合蛋白和RNA的致密聚集体。它们在应激条件下出现在细胞质中，并抑制mRNA翻译的起始。应激颗粒在应激条件下动态组装，应激消除后迅速解体。它们的RNA和蛋白质含量具有异质性，并且具有细胞类型和应激特异性。在不分裂的有丝分裂后神经元中，神经元应激颗粒的动态受到严格调控，这意味着它们的失调会导致神经退行性变。RNA结合蛋白的突变与应激颗粒有关。在许多神经退行性疾病中，如额颞叶痴呆和肌萎缩侧索硬化症，应激颗粒成分会在胞质内含物中积累。尽管应激颗粒主要介导细胞对应激的促生存适应性反应，但异常持续存在的应激颗粒可能会发展成聚集体，并与疾病的发病机制相关。在这篇综述中，我们介绍了神经元应激颗粒在生理学和病理学研究方面的最新进展，并讨论了去除与神经退行性变相关的异常、持续存在的应激颗粒的潜在治疗方法。
