| 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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| 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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