The disease mechanism and biomarker of ALS, the view from TDP-43 alternative splicing
| Project/Area Number |
17K09750
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥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 / 選択的スプライシング / バイオマーカー / ALS / TDP-43 / alternative splicing / biomarker |
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| Outline of Final Research Achievements |
We carried out TDP-43 mRNA alternative splicing (AS) analysis to elucidate the pathomechanism of amyotrophic lateral sclerosis (ALS). TDP-43 is a major component of inclusion body in ALS and is a key molecule of this disease. We found a unique TDP-43 mRNA AS pattern in neural tissue from ALS autopsied cases. Furthermore, the protein derived from the AS mRNA showed easy aggregation property. The same AS pattern was also found in the cerebellum, which is a non-injured tissue of ALS, but no difference was found in the blood cell mRNA from the control group, and it was not established as a biomarker.
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| Academic Significance and Societal Importance of the Research Achievements |
ALSの治療が困難な理由として、その病態機序が不明なこと、早期診断が困難なこと、がんにおける腫瘍マーカーのようなバイオマーカーが確立していないことがあげられる。本研究で解析した、TDP-43 mRNA の特異な選択的スプライシングパターンは、ALSの病態機序解明やバイオマーカーの確立に寄与する可能性がある。
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Report
(4 results)
Research Products
(9 results)
