2019 Fiscal Year Final Research Report
Elucidation of the mechanism of ALS exacerbation through abnormal activation of the TDP-43 ectopic promoter.
| Project/Area Number |
17K14967
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ALS / TDP-43 / プロモーター |
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| Outline of Final Research Achievements |
TDP-43 is thought to be one of the genes responsible for ALS, and it is a mutation in the TDP-43 gene. The characteristic pathology of TDP-43 is also found in patients with ALS who do not have TDP-43. This study focused on the transcriptional regulatory function of TDP-43 and analyzed its function. Our results show that the promoter activity of TDP-43 was detected experimentally for the first time upstream of the transcriptional start site of TDP-43.We also found that the promoter activity was ectopic to the original promoter. In addition, the TDP-43 splice variant does not affect the upstream promoter of TDP-43 and the different It was found to activate only the locative promoter. The results of the research period were presented at Neuro2019.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
TDP-43は1995年に転写調節因子として同定されたが、その後標的RNAの安定性やスプライシングを調節する機能が明らかとなり、これらの機能を介して自己発現量調節を行っていることが示された。2006年にTDP-43とALS病態との関与が初めて示唆されTDP-43の機能解析が活発となったが、TDP-43が転写を自己調節する可能性には着目されていなかった。本研究によりTDP-43が自己のプロモーターに結合し活性を抑制することがわかり、TDP-43の転写調節機能とALS病態の関与について今後着目する意義があると考える。国際学会における成果発表を通して、国内外の研究チームに研究意義を示すことができた。
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