Role of purine nucleotide receptor signaling in P. falciparum invasion of erythrocytes.

Research Project

Project/Area Number	18K08450
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54030:Infectious disease medicine-related
Research Institution	Tokyo Women's Medical University
Principal Investigator	Koshino Ichiro 東京女子医科大学, 医学部, 講師 (80328377)
Co-Investigator(Kenkyū-buntansha)	新敷信人東京女子医科大学, 医学部, 助教 (80569658)
Project Period (FY)	2018-04-01 – 2024-03-31
Project Status	Completed (Fiscal Year 2023)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	マラリア / 赤血球 / cAMP / マラリア原虫 / PKAリン酸化 / 情報伝達 / 感染防御 / ATP受容体
Outline of Final Research Achievements	Malaria is one of the major three infectious diseases in the world, caused by infection by malaria parasites. This study was conducted to examine if ATP-mediated intracellular signaling in host erythrocytes is critical in parasite infection, and to establish the basis for therapeutic strategy to prevent the parasite invasion of erythrocytes by interrupting the signaling pathway. Contrary to the expectation, all reagents examined which interrupt ATP-mediated signaling failed to inhibit parasite invasion. However, several reagents that leads to elevation in intracellular cyclic AMP level inhibited parasite invasion. These findings give some basis for therapeutic strategy by increasing cyclic AMP level exclusively in erythrocytes.
Academic Significance and Societal Importance of the Research Achievements	世界規模での精力的な研究にも関わらずマラリアが甚大な人的被害をもたらし続けている理由は、マラリア原虫の高頻度な遺伝子変異による薬剤耐性の獲得である。遺伝子変異の恐れが全くない宿主赤血球を標的とし、細胞内サイクリックAMP濃度を上昇させることによってマラリア原虫の感染を抑制できることを示した本研究の成果は、薬剤耐性の発生が事実上起こり得ない全く新規の治療法を確立するための基盤となる非常に重要な知見である。