| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Research Abstract |
TDP-43-positive inclusions in lower motor neurones of sporadic Amyotrophic lateral sclerosis (SALS) patients were immunopositive for Smurf2 and pSmad2/3. In contrast, TDP-43-positive inclusions in the extramotor neurones in the brain of SALS patients were noticeably negative for Smurf2 and pSmad2/3. These results demonstrated that the composition of the TDP-43 inclusions is regionally distinct, suggesting different underlying pathogenic processes. We replicated cytoplasmic aggregates of TDP-43 in HEK293T cells by transfecting the cells with a nuclear localization signal deletion mutant of TDP-43 and inhibiting proteasome activity. Overexpression of Smad2 reduced the amount of cytoplasmic aggregates in HEK293T cells, and TGF beta stimulation augmented this reduction effect in a dose-dependent manner. Our results suggest that activation of TGF beta/Smad signaling system may be a potential therapeutic approach to delay the progression of ALS.
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