| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| 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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