TDP-43的概况

The long and the short of TDP-43.

作者信息

Shenouda Marc, McKeever Paul M, Robertson Janice

机构信息

Tanz Centre for Research in Neurodegenerative Diseases, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

出版信息

Trends Neurosci. 2025 May;48(5):313-314. doi: 10.1016/j.tins.2025.03.003. Epub 2025 Mar 24.

DOI:10.1016/j.tins.2025.03.003

PMID:40133096

Abstract

In a recent study, Dykstra and colleagues show that shortened TAR DNA Binding Protein 43 (sTDP-43) isoforms are generated as by-products of TDP-43 autoregulation. sTDP-43 levels are regulated through nonsense-mediated decay and proteasomal and autophagic degradation, and elicit toxicity through dominant negative effects on TDP-43 splicing activity. These results identify mechanisms contributing to sTDP-43 accumulation and toxicity in disease.

摘要

在最近的一项研究中，戴克斯特拉及其同事表明，缩短的TAR DNA结合蛋白43（sTDP-43）亚型是TDP-43自身调节的副产物。sTDP-43水平通过无义介导的衰变、蛋白酶体和自噬降解来调节，并通过对TDP-43剪接活性的显性负效应引发毒性。这些结果确定了导致疾病中sTDP-43积累和毒性的机制。