The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis.
The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis.
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DOI：
10.1007/s00401-020-02203-0
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发表时间：
2020-11
影响因子：
12.7
通讯作者：
Gatt A
中科院分区：
文献类型：
--
作者：
Bampton A;Gittings LM;Fratta P;Lashley T;Gatt A
RNA代谢失调正在成为额颞叶痴呆（FTD）和肌萎缩侧索硬化（ALS）临床、遗传和病理重叠疾病发病机制的重要基础。异质性核核糖核蛋白（hnRNP）包括一个家族的RNA结合蛋白，在mRNA加工的各个方面具有不同的，多功能的作用。这些蛋白质在神经变性中的作用还远未被理解。在这里，我们回顾了一些统一的机制，hnRNP已直接或间接与FTD/ALS的发病机制，包括其纳入病理夹杂物和他们最知名的前mRNA剪接调控的作用。我们还讨论了更广泛的功能hnRNP，包括其作用的隐蔽外显子抑制，应力颗粒组装和协调的DNA损伤反应，这都是新兴的致病主题，在这两种疾病。然后，我们提出了一个综合模型，描绘了广泛的网络的致病事件可以从下降水平的功能hnRNP，不充分补偿的自动调节手段。最后，我们提供了一个全面的概述功能最相关的细胞作用，在FTD/ALS发病机制的背景下，hnRNP A1-U。
Dysregulated RNA metabolism is emerging as a crucially important mechanism underpinning the pathogenesis of frontotemporal dementia (FTD) and the clinically, genetically and pathologically overlapping disorder of amyotrophic lateral sclerosis (ALS). Heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a family of RNA-binding proteins with diverse, multi-functional roles across all aspects of mRNA processing. The role of these proteins in neurodegeneration is far from understood. Here, we review some of the unifying mechanisms by which hnRNPs have been directly or indirectly linked with FTD/ALS pathogenesis, including their incorporation into pathological inclusions and their best-known roles in pre-mRNA splicing regulation. We also discuss the broader functionalities of hnRNPs including their roles in cryptic exon repression, stress granule assembly and in co-ordinating the DNA damage response, which are all emerging pathogenic themes in both diseases. We then present an integrated model that depicts how a broad-ranging network of pathogenic events can arise from declining levels of functional hnRNPs that are inadequately compensated for by autoregulatory means. Finally, we provide a comprehensive overview of the most functionally relevant cellular roles, in the context of FTD/ALS pathogenesis, for hnRNPs A1-U.
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影响因子：
--
作者：
Andersson MK;Ståhlberg A;Arvidsson Y;Olofsson A;Semb H;Stenman G;Nilsson O;Aman P
通讯作者：
Aman P
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
影响因子：
7.7
作者：
Attig, Jan;Mozos, Igor Ruiz de los;Ule, Jernej
通讯作者：
Ule, Jernej
“神秘”外显子揭示了他们的一些秘密。
影响因子：
7.7
作者：
Calarco JA
通讯作者：
Calarco JA
影响因子：
14.9
作者：
Barreau C;Paillard L;Osborne HB
通讯作者：
Osborne HB