Role of molecular chaperone protein in aggregation of misfolded proteins

2015 Fiscal Year Final Research Report

• Project/Area Number: 24570143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• 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)
• Project Period (FY): 2012-04-01 – 2016-03-31
• 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

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.

Free Research Field

生物科学・構造生物化学