SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025, Evry, France.
Department of Functional Genomics, Institute of Molecular Biology and Genetics, 150, Zabolotnogo Str., Kyiv, 03680, Ukraine.
Curr Neurol Neurosci Rep. 2018 Nov 8;18(12):107. doi: 10.1007/s11910-018-0914-7.
ᅟ: A hallmark of neurodegenerative diseases is the accumulation of cytoplasmic protein aggregates in neurons of affected subjects. Among recently identified elements of these aggregates are RNA-binding proteins (RBPs) involved in RNA metabolism and alternative splicing and have in common the presence of low complexity domains (LCD) that are prone to self-assemble and form aggregates. The mechanism of cytoplasmic protein aggregation remains elusive. Stress granules (SGs) that are micrometric RNA-protein assemblies located in the cytoplasm of cells exposed to environmental stress are suspected to play the role of seeds. The review sheds light on the recent experimental results that suggest a link between SGs and cytoplasmic protein aggregates but also propose other routes for the formation of these aggregates. PURPOSE OF REVIEW: To analyze the potential relationship between cytoplasmic protein aggregates in neurons of affected subjects and stress granules. RECENT FINDINGS: Liquid phase separation explains how protein and RNA could assemble in membraneless compartments, notably SGs. These results highlight the importance of RBPs with LCD in the SG assembly. Maturation of SGs and in particular the dense core is a potential source of insoluble protein aggregates. Several lines of evidence linked stress granule dynamics to pathogenic protein aggregates. (i) Proteins that accumulate in cytoplasmic aggregates are also SG components. (ii) Neurons are specifically exposed to stress events due to their high metabolism and long lifespan. (iii) Diseases linked protein mutations affect the SG dynamics. (iv) SG dense core could be a breeding ground for protein aggregates. However, we should also keep in mind that SGs are not the only RNA-protein assembly in the cytoplasm; the RNA transport granules could also play a role in the formation of insoluble protein aggregates.
神经退行性疾病的一个标志是受影响受试者神经元中细胞质蛋白聚集体的积累。在最近鉴定的这些聚集体的元素中，有参与 RNA 代谢和选择性剪接的 RNA 结合蛋白 (RBP)，它们的共同特点是存在易于自我组装并形成聚集体的低复杂度结构域 (LCD)。细胞质蛋白聚集体的形成机制仍然难以捉摸。应激颗粒 (SGs) 是位于细胞细胞质中暴露于环境应激的 RNA-蛋白质微米级组装体，被怀疑起种子的作用。该综述阐明了最近的实验结果，这些结果表明 SGs 与细胞质蛋白聚集体之间存在联系，但也提出了这些聚集体形成的其他途径。
分析受影响受试者神经元中细胞质蛋白聚集体与应激颗粒之间的潜在关系。
液-液相分离解释了蛋白质和 RNA 如何在无膜隔间中组装，特别是 SGs。这些结果强调了具有 LCD 的 RBP 在 SG 组装中的重要性。SG 的成熟，特别是致密核心，是不溶性蛋白聚集体的潜在来源。应激颗粒动力学与致病性蛋白聚集体之间的几种联系的证据。(i) 在细胞质聚集体中积累的蛋白质也是 SG 成分。(ii) 由于代谢活跃和寿命长，神经元特别容易受到应激事件的影响。(iii) 与疾病相关的蛋白突变影响 SG 动力学。(iv) SG 致密核心可能是蛋白聚集体的滋生地。然而，我们还应该记住，SGs 不是细胞质中唯一的 RNA-蛋白质组装体；RNA 运输颗粒也可能在不溶性蛋白聚集体的形成中发挥作用。
