TAR DNA 结合蛋白 43 寡聚物在生理和病理中的作用。

TAR DNA-binding protein 43 oligomers in physiology and pathology.

机构信息

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Cheng Kung University and Academia Sinica, Taipei, Taiwan.

出版信息

IUBMB Life. 2022 Aug;74(8):794-811. doi: 10.1002/iub.2603. Epub 2022 Feb 28.

DOI:10.1002/iub.2603

PMID:35229461

Abstract

TAR DNA-binding protein 43 (TDP-43) is an RNA/DNA-binding protein involved in RNA regulation and diseases. In 2006, TDP-43 inclusions were found in the disease lesions of several neurodegenerative diseases. It is the pathological hallmark in both amyotrophic lateral sclerosis and frontotemporal lobar dementia. It also presents in a large portion of patients with Alzheimer's disease. TDP-43 is prone to aggregate; however, the role of TDP-43 oligomers remains poorly understood in both physiological and pathological conditions. In this review, we emphasize the role of oligomeric TDP-43 in both physiological and pathological conditions and discuss the potential mechanisms of oligomer formation. Finally, we suggest therapeutic strategies against the TDP-43 oligomers in neurodegenerative diseases.

摘要

TAR DNA 结合蛋白 43（TDP-43）是一种参与 RNA 调节和疾病的 RNA/DNA 结合蛋白。2006 年，在几种神经退行性疾病的病变中发现了 TDP-43 包含物。它是肌萎缩侧索硬化症和额颞叶痴呆的病理标志。它也存在于大部分阿尔茨海默病患者中。TDP-43 容易聚集；然而，在生理和病理条件下，TDP-43 低聚物的作用仍知之甚少。在这篇综述中，我们强调了低聚 TDP-43 在生理和病理条件下的作用，并讨论了低聚物形成的潜在机制。最后，我们提出了针对神经退行性疾病中 TDP-43 低聚物的治疗策略。