2021 Fiscal Year Final Research Report
Mechanism and regulation of protein aggregation in complicated cellular systems
| Project Area | Chemical Approaches for Miscellaneous / Crowding Live Systems |
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| Project/Area Number |
17H06352
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Osaka University |
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Principal Investigator |
Goto Yuji 大阪大学, 国際医工情報センター, 特任教授 (40153770)
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| Co-Investigator(Kenkyū-buntansha) |
茶谷 絵理 神戸大学, 理学研究科, 准教授 (00432493)
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| Project Period (FY) |
2017-06-30 – 2022-03-31
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| Keywords | 蛋白質 / 生体分子 / 老化 / 蛋白質凝集 / アミロイド線維 / 過飽和 / 溶解度 / 相転移 |
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| Outline of Final Research Achievements |
Amyloid fibrils are ordered aggregates of denatured proteins associated with amyloidosis. By studying amyloid formation of various proteins, we showed that amyloid fibrils form above solubility by breaking supersaturation.
To clarify the mechanism of dialysis-related amyloidosis, we studied the effects of sera on beta2-microglobulin amyloid formation. Although sera inhibited amyloid formation, the inhibitory effects were weaker for sera collected from dialysis patients. When sera collected before and after maintenance dialysis treatments were compared, the latter inhibited amyloid formation more than the former. The results indicated that, although the inhibitory were deteriorated in dialysis patients, they were ameliorated by maintenance dialysis treatments. Among serum components, serum albumin prevented amyloid formation based on macromolecular crowding effects. The model constructed assuming accumulative effects of risk factors will be useful for predicting the onset of disease.
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| Free Research Field |
蛋白質科学
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| Academic Significance and Societal Importance of the Research Achievements |
透析アミロイドーシスやパーキンソン病などのアミロイドーシスは高齢化社会の深刻な問題であるが、それらの発症原理については不明な点が多い。本研究では、アミロイドーシス発症の原因物質であるアミロイド線維の形成が、溶解度や過飽和といった物理化学の基本原理に基づいて理解できることを明らかにした。さらに、細胞内外の夾雑系がアミロイド線維の形成を阻害し、ひいてはアミロイドーシス発症を抑制していることを示した。
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