Mechanism of fibril formation of human lysozyme mutants and analysis of its toxicity in the amyloid disease model mice
| Project/Area Number |
25450476
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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 |
Integrative animal science
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| Research Institution | Kagoshima University |
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Principal Investigator |
Sugimoto Yasushi 鹿児島大学, 農水産獣医学域農学系, 教授 (10100736)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | リゾチーム / アミロイド線維 / 分子シャペロン / 小胞体ストレス / GRP78/BiP / トランスサイレチン / トランスジェニックマウス / アミロイド病 / 変異体 / フォールディング / ＥＲストレス / ＵＰＲ / アミロイドーシス / タンパク質凝集体 / アポトーシス |
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| Outline of Final Research Achievements |
The toxicity of the human lysozyme mutants that cause a systemic amyloidosis could be verified at the cellular level and the biological level. Lysozyme mutants accumulate in the endoplasmic reticulum, remaining bound to molecular chaperone GRP78 / BiP. The accumulation of both proteins result in activating the IRE1-XBP1-GRP78 / BiP pathway, which induces endoplasmic reticulum stress. Transthyretin mutants accumulated in the endoplasmic reticulum and activated the IRE1-XBP1-GRP78 / BiP pathway and induced ER stress as well as lysozyme. Furthermore, transthyretin mutants remained bound to GRP78 / BiP. Amyloidosis caused by abnormal secreted proteins might have in common. Aggregating proteins tend to form amyloid fibrils and accumulate in the endoplasmic reticulum and provide damage for cell. Cell damage lead to loss of the cell function and cell death. In conclusion, amyloidosis of lysozyme is assumed to be caused by the accumulation of abnormal protein in the cell over long period.
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Report
(4 results)
Research Products
(15 results)
