期刊
NEUROSCIENCE RESEARCH
卷 107, 期 -, 页码 63-69出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neures.2015.12.006
关键词
TDP-43; Calpain; AMPA receptor; GluA2; RNA editing; Adenosine deaminase acting on RNA 2 (ADAR2); Amyotrophic lateral sclerosis (ALS)
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [23790977, 25461269, 22390173]
- Grants-in-Aid for Scientific Research [23790977, 22390173, 25461269, 25461266] Funding Source: KAKEN
TAR DNA-binding protein-43 (TDP-43) pathology, which includes the presence of abnormal TDP-43-containing inclusions with a loss of nuclear TDP-43 in affected neurons, is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and/or frontotemporal lobar degeneration (FTLD). TDP-43 in the pathological brains and spinal cords of ALS/FTLD patients is abnormally fragmented and phosphorylated. It is believed that the generation of aggregation-prone TDP-43 fragments initiates TDP-43 pathology, and we previously reported that calpain has an important role in the generation of such aggregation prone TDP-43 fragments. However, the role of phosphorylation in TDP-43 pathology has not been largely elucidated, despite previous observations that several kinases and their kinases are involved in TDP-43 phosphorylation. Here, we investigated the role of TDP-43 phosphorylation in the calpain-dependent cleavage of TDP-43 and found that phosphorylated, full-length TDP-43 and calpain-dependent TDP-43 fragments were more resistant to cleavage by calpain than endogenous full-length TDP-43 was. These results suggest that both phosphorylated and calpain-cleaved TDP-43 fragments persist intracellularly for a length of time that is sufficient for self-aggregation, thereby serving as seeds for inclusions. (C ) 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据