2015 Fiscal Year Final Research Report
Analysis of the molecular link of amyotrophic lateral sclerosis associated genes in sporadic ALS model mice
Project/Area Number |
25461269
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | The University of Tokyo |
Principal Investigator |
Yamashita Takenari 東京大学, 医学(系)研究科(研究院), 特任研究員 (20431843)
|
Co-Investigator(Renkei-kenkyūsha) |
KWAK Shin 東京大学, 大学院医学系研究科, 客員研究員 (40160981)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Keywords | 筋萎縮性側索硬化症 / カルパイン / RNA編集 / カルシウム / TDP-43 / ADAR2 / AMPA受容体 / リン酸化 |
Outline of Final Research Achievements |
We found that ADAR2-negative motor neurons in the spinal cord showed TDP-43 pathology, or subcellular mislocalization of TDP-43, in the conditional ADAR2 knockout (AR2) mice, a mechanistic ALS model in which the ADAR2 gene was targeted in cholinergic neurons including motor neurons. TDP-43 pathology in the ADAR2-lacking motor neurons in the AR2 mice was caused by abnormal activation of calpain, a Ca2+-dependent cysteine protease. We revealed several calpain-dependent cleavage sites in the C-terminal region of TDP-43. Moreover, we 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.
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Free Research Field |
内科系臨床医学・神経内科学
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