Structurally distinct alpha-synuclein fibrils induce robust Parkinsonian pathology
| Project/Area Number |
16K19512
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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 |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
Hayakawa Hideki 大阪大学, 医学系研究科, 特任研究員 (70468594)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | パーキンソン病 / alpha-synuclein / α-synuclein / 多系統萎縮症 / オリゴデンドロサイト / 脳神経疾患 / 脳・神経 |
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| Outline of Final Research Achievements |
Alpha-synuclein (α-syn) is a major component of Lewy bodies, which are the pathological hallmark in Parkinson’s disease, and its genetic mutations cause familial forms of Parkinson’s disease. Patients with α-syn G51D mutation exhibit severe clinical symptoms. We studied the mechanisms associated with severe neurotoxicity of α-syn G51D mutation using a murine model generated by G51D α-syn fibril injection into the brain. We found that G51D α-syn fibrils have higher β-sheet contents than wild-type α-syn fibrils. The addition of G51D α-syn fibrils to mammalian cells overexpressing α-syn resulted in the formation of phosphorylated α-syn inclusions at a higher rate. Similarly, an injection of G51D α-syn fibrils into the substantia nigra of a mouse brain induced more widespread phosphorylated α-syn pathology.
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病(PD)は神経変性疾患の中でアルツハイマー病についで2番目に多く、高齢化社会を迎える本邦に限らず、世界的に患者数の増加が予想される。現状では有効な予防法や根治療法はなく、その病態の解明と治療法の開発は医学研究の急務となっている。PDの治療研究における問題点は、病態を反映した優れたPDモデルが無いことであった。そのために、治療開発が大きく遅れており、その開発が急務である。我々は変異αシヌクレイン(αsyn) fibrilを用い、リン酸化αsyn(p-αsyn)凝集と黒質ドパミン(DA)神経細胞の変性脱落、それに伴う運動機能低下を有意に認める新規PDモデルマウスを作成し報告した。
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Report
(5 results)
Research Products
(9 results)
