過飽和の解消による蛋白質の異常凝集体の形成に関する研究

2016 Fiscal Year Annual Research Report

• Project/Area Number: 14J04433
• Research Institution: Osaka University
• Principal Investigator: 林 雨曦 大阪大学, 理学研究科, 特別研究員(DC1)
• Project Period (FY): 2014-04-25 – 2017-03-31
• Keywords: protein aggregation / supersaturation

Outline of Annual Research Achievements

I extended my study on protein aggregation from globular proteins to an intrinsically disordered protein, amyloid beta 1-40, this year. Misfolding and aggregation of amyloid beta 1-40 has been related to the onset of Alzheimer’s disease. Although much has been done to explore amyloid beta 1-40 aggregation, its detail mechanism is only partially understood.
I investigated the microscopic mechanism and pathway of amyloid beta 1-40 aggregation with macroscopic viewpoints using alcohols with the application of ultrasonication. The results suggested that the microscopic aggregation pathways of amyloid beta 1-40 depended on concentration and type of alcohols. Moreover, the addition of salts induced conversion of amyloid beta 1-40 from off-pathway oligomers into in-pathways protofibrils. Based on experimental results, I constructed phase diagrams of amyloid beta 1-40 aggregation in alcohols, which indicated that the concept of solubility and supersaturation also provided a macroscopic understanding of amyloid beta 1-40 aggregation.
In conclusion, these results gave a further insight into the aggregation process of amyloid beta 1-40, which is beneficial for developing small molecules to control amyloid beta 1-40 aggregation.

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Energetic Basis on Interactions between Ferredoxin and Ferredoxin NADP+ Reductase at Varying Physiological Conditions (2017)
  • Author(s): Kinoshita M., Kim JY., Kume S., Lin Y., Mok H., Kataoka Y., Ishimori K., Markova N., Kurisu G., Hase T., and Lee YH
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 482 Pages: 909, 915
  • DOI: 10.1016/j.bbrc.2016.11.132
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Amorphous aggregation of cytochrome c with inherently low amyloidogenicity is characterized by the phase diagram (2016)
  • Author(s): Lin Y., Kardos J., Kinoshita M., Sugiki T., Ishimori K., Goto Y., and Lee YH.
  • Organizer: The 54th Annual Meeting of the Biophysical Society of Japan
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2016-11-25 – 2016-11-27