Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Outline of Final Research Achievements |
We investigated effect of molecular chaperone protein on aggregation of misfolded proteins, which is considered to cause various diseases including Alzheimer’s disease (AD). Prefoldin (PFD) is a chaperone that captures unfolded proteins and delivers them to chaperonin for functional folding. We found that human PFD (hPFD) inhibited amyloidβ (Aβ) fibrillation and induced formation of soluble Aβ oligomers, which showed lower cell toxicity and different surface structure compared with toxic oligomers. These results suggest a relation between cytotoxicity of Aβ oligomers and structure. We also demonstrated that hPFD could prevent aggregation of polyglutamine (polyQ) that causes Huntington disease, and could protect neuronal cells from polyQ toxicity. It was also found that small heat shock protein (sHsp) from yeast could induce formation of less-toxic Aβ aggregates, suggesting a possible protective role of sHsp in disease pathology.
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