| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
To elucidate the pathomechanism of TDP-43, we carried out RNA-seq analysis and found that Atg1 and several authophgic geneswere upregulated in the brain of TDP-43 transgenic (tg) fly. Knockdown of Atg1 rescued the retinal degeneration of TDP-43 tg fly, suggesting that autophagic pathway is involved in the pathogenesis of TDP-43. Moreover, we found that TDP-43 specifically intedacted with ULK1 mRNA in Neuro-2a cells and that knockdown of TDP-43 reduced the expression level of ULK1 protein, suggesting that TDP-43 regulates autophagic pathway via regulating the expression of ULK1.
By the analysis of the ALS-related genes, we found that overexpression of CREST induced neurodegeneration in the retina of tg fly, that familial ALS-linked mutations in Profilin1 cause the neurodegenetaion through the sequestration of TDP-43 into cytoplasm, and that self-assembly of FUS via its lox-complexity domain contributes neurodegeneration induced by FUS.
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