Molecular, functional, and pathological aspects of TDP-43 fragmentation.
Molecular, functional, and pathological aspects of TDP-43 fragmentation.
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TDP-43断裂的分子、功能和病理学方面。
DOI：
10.1016/j.isci.2021.102459
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发表时间：
2021-05-21
期刊：
影响因子：
5.8
通讯作者：
Rincon-Limas DE
中科院分区：
文献类型：
--
作者：
Chhangani D;Martín-Peña A;Rincon-Limas DE
TDP-43 （Transactive response DNA binding protein 43）是一种参与转录调控和RNA加工的DNA/RNA结合蛋白。它与散发性和家族性肌萎缩性侧索硬化症和额颞叶变性有关。TDP-43主要是细胞核，但在病理条件下它会转移到细胞质中。胞质积累、磷酸化、泛素化和截断是TDP-43蛋白病变的主要标志。在这些过程中，导致TDP-43破碎的途径仍然知之甚少。本文综述了几种TDP-43片段的分子和生化特性，介导其产生的机制和因素，以及它们在疾病进展中的潜在作用。我们还研究了TDP-43 c端片段在包括阿尔茨海默病在内的几种神经系统疾病中的存在，并强调了它们各自的意义。最后，我们讨论了表达TDP-43片段的动物模型的特征以及最近针对TDP-43截断的治疗策略。TDP-43片段可能有助于功能丧失和功能获得机制蛋白水解和选择性剪接可导致TDP-43截断ALS/FTLD以外的几种神经系统疾病显示TDP-43片段，TDP-43片段的确切生物学和病理作用尚不清楚；分子生理学;分子生物学;分子间相互作用;
Transactive response DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in transcriptional regulation and RNA processing. It is linked to sporadic and familial amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 is predominantly nuclear, but it translocates to the cytoplasm under pathological conditions. Cytoplasmic accumulation, phosphorylation, ubiquitination and truncation of TDP-43 are the main hallmarks of TDP-43 proteinopathies. Among these processes, the pathways leading to TDP-43 fragmentation remain poorly understood. We review here the molecular and biochemical properties of several TDP-43 fragments, the mechanisms and factors mediating their production, and their potential role in disease progression. We also address the presence of TDP-43 C-terminal fragments in several neurological disorders, including Alzheimer's disease, and highlight their respective implications. Finally, we discuss features of animal models expressing TDP-43 fragments as well as recent therapeutic strategies to approach TDP-43 truncation. TDP-43 fragments may contribute to loss- and gain-of-function mechanisms Proteolysis as well as alternative splicing can lead to TDP-43 truncation Several neurological conditions beyond the ALS/FTLD spectrum display TDP-43 fragments The precise biological and pathological roles of TDP-43 fragments are unknown Biological sciences; Molecular physiology; Molecular biology; Molecular interaction;
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影响因子：
25
作者：
Chou CC;Zhang Y;Umoh ME;Vaughan SW;Lorenzini I;Liu F;Sayegh M;Donlin-Asp PG;Chen YH;Duong DM;Seyfried NT;Powers MA;Kukar T;Hales CM;Gearing M;Cairns NJ;Boylan KB;Dickson DW;Rademakers R;Zhang YJ;Petrucelli L;Sattler R;Zarnescu DC;Glass JD;Rossoll W
通讯作者：
Rossoll W
影响因子：
14.8
作者：
Barmada, Sami J.;Serio, Andrea;Arjun, Arpana;Bilican, Bilada;Daub, Aaron;Ando, D. Michael;Tsvetkov, Andrey;Pleiss, Michael;Li, Xingli;Peisach, Daniel;Shaw, Christopher;Chandran, Siddharthan;Finkbeiner, Steven
通讯作者：
Finkbeiner, Steven
影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.
影响因子：
2.1
作者：
Ferrari R;Kapogiannis D;Huey ED;Momeni P
通讯作者：
Momeni P
影响因子：
3.5
作者：
Crippa V;Cicardi ME;Ramesh N;Seguin SJ;Ganassi M;Bigi I;Diacci C;Zelotti E;Baratashvili M;Gregory JM;Dobson CM;Cereda C;Pandey UB;Poletti A;Carra S
通讯作者：
Carra S