期刊
NEUROSCIENCE
卷 287, 期 -, 页码 113-124出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2014.12.007
关键词
amyotrophic lateral sclerosis; frontotemporal lobar degeneration; fused in sarcoma; transactive response DNA-binding protein-43
资金
- Japan Society for the Promotion of Science [23390059, 25460342]
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- Tokyo Medical University Research Grant
- Grants-in-Aid for Scientific Research [25460342, 23390059] Funding Source: KAKEN
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative diseases that overlap clinically, genetically, and pathologically. Dysregulation of fused in sarcoma (FUS) has been hypothesized to cause ALS and FTLD in gain-of-function and/or loss-of-function manners. However, the link between the pathogenesis of ALS/FTLD and dysfunction of FUS has not been clearly determined. In this study, we found that overexpression of FUS, but not knocking-down of endogenous FUS expression, induces death in motor neuronal NSC34 cells and primary cortical neurons via the mitochondrial apoptotic pathway, possibly independently of transactive response DNA-binding protein-43. Furthermore, we found that nuclear FUS, but not cytoplasmic FUS, is responsible for FUS-induced neuronal cell death. These observations suggest that the gain-of-function of FUS in the nucleus contributes to the pathogenesis of FUS-linked neurodegenerative diseases. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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