2018 Fiscal Year Final Research Report
Development of in vitro amyloid fibril formation systems that mimic the physiological fibrillogenesis conditions in vivo and their application to the analysis of fibril formation mechanism
| Project/Area Number |
15K06965
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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 |
Structural biochemistry
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内木 宏延 福井大学, 学術研究院医学系部門, 教授 (10227704)
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| Research Collaborator |
Endo Yoshinori
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | 蛋白質 / 変性とフォールディング / 病理学 / アミロイド / アルツハイマー病 |
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| Outline of Final Research Achievements |
We evaluate the roles of the various biological molecules or reaction conditions in the amyloid fibril formation using amyloid fibril formation systems in vitro. (1) We examined the effects of apoE and clusterin on the fibril formation of Alzheimer’s disease amyloid β-peptide (Aβ) using the previously developed near-physiological Aβ fibril formation system for evaluating the efficiency of protein components to induce the nucleation of Aβ peptide. We found that physiological concentrations of apoE and clusterin delayed the initiation time of amyloid growth kinetics in a concentration-dependent manner. (2) To further decrease the concentration of Aβ peptide in the reaction, we developed a high-sensitive system, in which the elongation of amyloid fibrils by sub-micromolar concentrations of Aβ peptide can be detected. (3) We tried to identify the proteins which induce the nucleation of beta2-microglobulin amyloid, but the reaction system was not sufficient to detect them.
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| Free Research Field |
生物物理学
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病(AD)患者が急増しており、根本的な予防法・治療法の開発が急務である。Aβ蛋白質(Aβ)は、ADの病態の最上流部にあるとされている。アミロイド線維形成など、Aβの脳内での挙動を解明する為に、試験管内で正確に再現することが必要。現状では、脳内の生理濃度(nM)よりかなり高濃度のAβを用いて解析しており、反応機構の再現が不完全な可能性がある。より低濃度で反応する試験管内反応系を構築し、重合、オリゴマー形成、共存蛋白質群との相互作用などを正確に再現し、予防・治療法の開発に役立てる。β2-mアミロイドでも生体における重合機序が完全には解明されておらず、試験管内重合反応系の構築が必要。
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