| Project/Area Number |
22590932
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
NAGANO Seiichi 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第五部, 室長 (40362727)
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| Co-Investigator(Renkei-kenkyūsha) |
NAGAI Yoshitaka (独)国立精神・神経医療研究センター, 神経研究所疾病研究第四部, 室長 (60335354)
SUMI Hisae 大阪大学, 大学院医学系研究科, 助教 (30403059)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 筋萎縮性側索硬化症 / TDP-43 / RNA / 神経突起 |
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| Research Abstract |
Altered localization and abnormal deposition of TDP-43, a nuclear RNA-binding protein, into the cytoplasm of neurons are hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We hypothesized that deposition of TDP-43 may disturb the particular mRNA transport by the protein to neurites to develop ALS/FTLD, and identified mRNA associated with protein translation including that of ribosomal proteins as candidate targets transported to neurites by TDP-43 using our compartment culture system of cortical neurons. The target mRNA and TDP-43 co-localized and showed the same movement in neurites. Translation of the target mRNA was increased by stimulation with a local protein translation stimulator, BDNF, in neurites. Moreover, translation of the target mRNA in neurites was decreased by down-regulation of TDP-43 expression, which caused the decrease of overall protein translation at the site and the inhibition of neurite outgrowth. It indicates that the failure of local protein translation may occur by loss-of-function of TDP-43 in neurites, which may be a factor of the neurodegeneration in ALS/FTLD.
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