| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Research Abstract |
Impairment of proteolytic machineries has been recognized to participate in motoneuron degeneration in ALS. Furthermore, recent identifications of disease-associated genes that include TDP-43 and FUS have led to open a new era in ALS research. We produced recombinant adenovirus encoding wild type and mutant TDP-43 or FUS, and those encoding shRNAs for proteosome(PSMC1), endosome/ESCRT(VPS24) and autophagy(ATG5) systems to investigate whether the coupled gene transductions in motoneurons elicit ALS pathology. Co-infections of adenovirus encoding shRNA for PSMC1 or ATG5 with TDP-43 or FUS adenovirus enhanced cytoplasmic aggregate formation in motoneurons, suggesting that impairment of proteasome, endosome/ESCRT, or autophagy system accelerates TDP-43 and FUS pathology in ALS.
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