| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Aberrant accumulation of TDP-43 or FUS in the affected motor neurons of patients with amyotrophic lateral sclerosis (ALS) is a pathological feature of ALS, however the molecular mechanisms whereby TDP-43 induced the neurodegeneration remained unclear. Here, we found that ULK1 mRNA was interacted with TDP-43, and knockdown of TDP-43 reduced the level of protein of ULK1. Knockdown of TDP-43 also reduced the level of LC3-II, indicating that TDP-43 has an important role in the regulation of autophagy. Moreover, ULK1 deficient mice exhibited severer motor dysfunction in the AAV9-TDP-43 model. These data suggest that autophagy regulates neurodegeneration induced by TDP-43.
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