2019 Fiscal Year Final Research Report
Research to elucidate novel molecular mechanism in Alzheimer's disease
| Project/Area Number |
17K10301
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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 |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | アルツハイマー病 / アミロイドβ / 疾患リスク遺伝子 / スプライシング / Omics |
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| Outline of Final Research Achievements |
Alzheimer's disease is a complex disease and the patients are heterogeneou. We have addressed this difficulty by noting that the susceptibility of Alzheimer's pathology to mouse strains varies greatly. We have identified KLC1 slice variant E as a regulator of the amount of Aβ accumulation by comprehensive gene research in mice. In this study, we found that the risk gene X (not open to the public) of Alzheimer's disease, whose function was unknown, strongly regulates KLC1 splicing. Omics study uncover the connection betseen Alzheimer risk gene X and KLC1. in vitro and in vivo studies confirmed the regulation of KLC1 splicing by gene X.
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| Free Research Field |
認知症
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病の新たな発症分子メカニズムを明らかにしつつある。伝子X(非公開）からKLC1のスプライシング異常を経てAβ病理が加速するというパスウエイである。ヒト剖検脳や末梢血のKLC1解析もこのパスウエイの存在を支持した。一連の発見は複雑なだけでなく不均一なアルツハイマー病患者の中に、特定の生物学的発症メカニズムをもつサブグループが存在することも意味する。アルツハイマー病患者群をKLC1パスウエイの異常の有無で細分類したうえでのKLC1パスウエイに対する治療法を開発は、これまでにない効率的な治療法開発戦略になると考える。
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