Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Outline of Final Research Achievements |
Abnormal deposition of an RNA-binding protein TDP-43 is a hallmark in neurons of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). We hypothesized that mRNA transport to neurites by TDP-43 is disturbed by deposition of the protein and failure of a specific mRNA transport is associated with ALS/FTLD-U pathogenesis, and identified mRNA of ribosomal proteins (Rp) as targets for TDP-43-mediated transport. We have proven in this study that Rp mRNA binds TDP-43 through its untranslated region and co-localizes with the protein in neurites. Down-regulation of TDP-43 expression disrupted neuritic extension and local ribosomal function. Moreover, exogenously introduced Rp was assembled into endogenous ribosomes.
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