Liquid-Liquid Phase Separation of TDP-43 and FUS in Physiology and Pathology of Neurodegenerative Diseases.
Liquid-Liquid Phase Separation of TDP-43 and FUS in Physiology and Pathology of Neurodegenerative Diseases.
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DOI：
10.3389/fmolb.2022.826719
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发表时间：
2022
影响因子：
5
通讯作者：
Guo L
中科院分区：
文献类型：
--
作者：
Carey JL;Guo L
RNA结合蛋白的液-液相分离介导了许多具有重要细胞功能的无膜细胞器的形成。然而，这些蛋白质的异常相变导致形成不溶性蛋白质聚集体，这是包括ALS和FTD在内的神经退行性疾病的病理学标志。TDP-43和FUS是两种这样的RNA结合蛋白，其在ALS和FTD患者中错误定位和聚集。它们具有相似的结构域结构，提供多价相互作用，驱动它们在体外和细胞环境中的相分离。在这篇文章中，我们综述了介导和调节TDP-43和FUS相分离的因素。我们还综述了TDP-43和FUS的相分离特性与其在细胞中的功能作用之间的关系。TDP-43和FUS的异常相变导致蛋白质聚集并破坏其正常细胞功能。因此，TDP-43和FUS的功能蛋白相的恢复可能对神经元细胞有益。我们讨论了TDP-43和FUS异常相变和聚集的可能机制，同时回顾了目前正在探索的减轻TDP-43和FUS异常相变和聚集的潜在治疗策略。
Liquid-liquid phase separation of RNA-binding proteins mediates the formation of numerous membraneless organelles with essential cellular function. However, aberrant phase transition of these proteins leads to the formation of insoluble protein aggregates, which are pathological hallmarks of neurodegenerative diseases including ALS and FTD. TDP-43 and FUS are two such RNA-binding proteins that mislocalize and aggregate in patients of ALS and FTD. They have similar domain structures that provide multivalent interactions driving their phase separation in vitro and in the cellular environment. In this article, we review the factors that mediate and regulate phase separation of TDP-43 and FUS. We also review evidences that connect the phase separation property of TDP-43 and FUS to their functional roles in cells. Aberrant phase transition of TDP-43 and FUS leads to protein aggregation and disrupts their regular cell function. Therefore, restoration of functional protein phase of TDP-43 and FUS could be beneficial for neuronal cells. We discuss possible mechanisms for TDP-43 and FUS aberrant phase transition and aggregation while reviewing the methods that are currently being explored as potential therapeutic strategies to mitigate aberrant phase transition and aggregation of TDP-43 and FUS.
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影响因子：
15.1
作者：
Baron DM;Kaushansky LJ;Ward CL;Sama RR;Chian RJ;Boggio KJ;Quaresma AJ;Nickerson JA;Bosco DA
通讯作者：
Bosco DA
影响因子：
16.6
作者：
Altman T;Ionescu A;Ibraheem A;Priesmann D;Gradus-Pery T;Farberov L;Alexandra G;Shelestovich N;Dafinca R;Shomron N;Rage F;Talbot K;Ward ME;Dori A;Krüger M;Perlson E
通讯作者：
Perlson E
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
影响因子：
4
作者：
Ayala, Youhna M.;Zago, Paola;Baralle, Francisco E.
通讯作者：
Baralle, Francisco E.
影响因子：
64.8
作者：
Arseni D;Hasegawa M;Murzin AG;Kametani F;Arai M;Yoshida M;Ryskeldi-Falcon B
通讯作者：
Ryskeldi-Falcon B