Examination of new therapies targeting alternative splicing abnormalities in neuropathic pain.
| Project/Area Number |
17K16758
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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 |
Anesthesiology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 神経障害性疼痛 / 選択的スプライシング / lncRNA / RNA結合タンパク / 疼痛関連lncRNA / RNA結合タンパク質 / 長鎖非コードRNA |
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| Outline of Final Research Achievements |
We found that alternative splicing patterns were significantly altered in the primary sensory neurons of neuropathic pain model animals, and that alternative splicing abnormalities may contribute to the pathology of neuropathic pain. It was revealed that expression changes of lncRNA, which is a major regulator of alternative splicing, following nerve injury cause expression changes of various genes involved in inflammation and neural function. Furthermore, it was suggested that lncRNA may contribute to neuropathic pain by regulating intracellular localization of many splicing regulatory proteins in the primary sensory neurons via binding to them.
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| Academic Significance and Societal Importance of the Research Achievements |
選択的スプライシング調節機構の破綻と疾患との関連性が重要視されているが、選択的スプライシングの異常から神経障害性疼痛に対する治療標的を探索する研究はほとんど報告がなかった。我々は従来、解析が困難とされていた選択的スプライシングの解析を次世代シーケンサーによる網羅的な遺伝子発現解析やウイルスベクターを利用することにより可能としてきた。また、今回の研究成果はスプライシング制御因子であるlncRNAを標的とするという全く新たな視点での疼痛の分子機構の解明への一助を担い、より包括的な疼痛の分子基盤の理解に基づいた治療法の開発に貢献できると考える。
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Report
(5 results)
Research Products
(8 results)
