Nup62 定位错误导致肌萎缩侧索硬化症/额颞叶变性中的 TDP-43 蛋白病。

Mislocalization of Nup62 Contributes to TDP-43 Proteinopathy in ALS/FTLD.

机构信息

Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong 793022, India.

Regional Director's Office, Indira Gandhi National Open University (IGNOU), Regional Centre Kohima, Kenuozou, Kohima 797001, India.

出版信息

ACS Chem Neurosci. 2022 Sep 7;13(17):2544-2546. doi: 10.1021/acschemneuro.2c00480. Epub 2022 Aug 24.

DOI:10.1021/acschemneuro.2c00480

PMID:36001801

Abstract

The nucleocytoplasmic transport (NCT) is impaired in C9-ALS/FTLD, a common genetically caused form of ALS and FTLD. The NCT is regulated by proteins called FG-nucleoporins (FG-Nups), with domains enriched in phenylalanine-glycine repeats. However, the relationship between FG-Nups and TDP-43, an RBP found to be mislocalized in ALS/FTLD patients, has not been defined. A recent study found that a critical protein, FG-Nup62, is mislocalized both and in diseased states. The mislocalized Nup62 was colocalized with TDP-43 in cytoplasmic inclusions and promoted its liquid-to-solid transition. The work highlights the involvement of Nup62 in the pathogenesis of ALS/FTLD and the interaction between Nup62 and TDP-43.

摘要

核质转运（NCT）在 C9-ALS/FTLD 中受损，这是一种常见的遗传性 ALS 和 FTLD 形式。NCT 受称为 FG-核孔蛋白（FG-Nups）的蛋白质调节，这些蛋白质富含苯丙氨酸-甘氨酸重复序列。然而，FG-Nups 与 TDP-43 之间的关系尚未确定，TDP-43 是一种在 ALS/FTLD 患者中发现定位错误的 RBP。最近的一项研究发现，一种关键蛋白 FG-Nup62 在疾病状态下发生了定位错误。定位错误的 Nup62 与细胞质包涵体中的 TDP-43 共定位，并促进其液-固转变。这项工作强调了 Nup62 在 ALS/FTLD 发病机制中的作用以及 Nup62 和 TDP-43 之间的相互作用。