Role of molecular chaperone protein in aggregation of misfolded proteins
Project/Area Number |
24570143
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Structural biochemistry
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Research Institution | Ehime University (2015) The Institute of Physical and Chemical Research (2012-2014) |
Principal Investigator |
ZAKO TAMOTSU 愛媛大学, 理工学研究科, 教授 (50399440)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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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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Keywords | アミロイド凝集 / 分子シャペロンタンパク質 / アルツハイマー病 / 一分子蛍光イメージング / プレフォルディン / スモールヒートショックプロテイン / アミロイド / タンパク質ミスフォールディング病 / 金ナノ粒子 / 高感度検出 / 一分子計測 |
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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Report
(5 results)
Research Products
(36 results)
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[Journal Article] Prefoldin protects neuronal cells from polyglutamine toxicity by preventing aggregation formation.2013
Author(s)
Tashiro E, Zako T, Muto H, Itoo Y, Sorgjerd K, Terada N, Abe A, Miyazawa M, Kitamura A, Kitaura H, Kubota H, Maeda M, Momoi T, Iguchi-Ariga SM, Kinjo M, Ariga H.
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Journal Title
Journal of Biological Chemistry
Volume: 288
Issue: 27
Pages: 19958-19972
DOI
NAID
Related Report
Peer Reviewed
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