Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?
Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?
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DOI：
10.3389/fncel.2015.00423
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发表时间：
2015
影响因子：
5.3
通讯作者：
Vande Velde C
中科院分区：
文献类型：
--
作者：
Aulas A;Vande Velde C
应激颗粒（SGs）是在应激条件下形成的含有RNA的细胞质病灶。自1999年发现以来，已有超过120种蛋白质被描述定位于这些结构（在154篇出版物中）。这些组分中的大多数是RNA结合蛋白（RBP）或参与RNA代谢和翻译。SG与多种病理学有关，包括炎性疾病、癌症、病毒感染和神经退行性疾病，如肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTD）。在ALS和FTD中，大多数病例没有已知的病因，暴露于外部应激通常被认为是疾病开始或疾病进展速度的贡献者。值得注意的是，ALS和FTD都以病理性包涵体为特征，其中一些众所周知的SG标志物定位于ALS相关蛋白TDP-43和FUS。我们认为TDP-43和FUS在疾病发病机制中是遗传易感性和环境应激暴露之间的界面。在这里，我们将讨论TDP-43和FUS在SG动力学中的作用，以及疾病相关突变如何影响这一过程。
Stress granules (SGs) are RNA-containing cytoplasmic foci formed in response to stress exposure. Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications). Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation. SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS and FTD, the majority of cases have no known etiology and exposure to external stress is frequently proposed as a contributor to either disease initiation or the rate of disease progression. Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS. We propose that TDP-43 and FUS serve as an interface between genetic susceptibility and environmental stress exposure in disease pathogenesis. Here, we will discuss the role of TDP-43 and FUS in SG dynamics and how disease-linked mutations affect this process.