Study on the mechanism of paclitaxel-induced peripheral neuropathy by Mitofusin2

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16101
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Fukuoka University
• Principal Investigator: Yamashita Yuta 福岡大学, 薬学部, 助教 (90823964)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: パクリタキセル / 末梢神経障害 / mitofusin 2

Outline of Final Research Achievements

Focusing on mitofusin 2 (Mfn2), I investigated the mechanisms and treatments of paclitaxel (PTX)-induced peripheral neuropathy. PTX inhibited neurite outgrowth and decreased MFN2 expression in F11 dorsal root ganglia × mouse neuroblastoma cells. However, I was unable to clarify whether MFN2 is involved in neurite outgrowth inhibition. Moreover, BAPTA-AM and cyclosporin A, both of which are therapeutic candidates, had no effect on PTX-induced inhibition of neurite outgrowth and reduction of Mfn2 expression.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

PTXは培養細胞に対して神経様突起伸長阻害とMfn2の発現量低下を引き起こした。このことは、PTX誘発性末梢神経障害モデルラットで起きた現象を細胞実験で模倣可能である事を示唆する。よって本結果は、培養細胞がPTX誘発性末梢神経障害における病態解明や治療候補薬スクリーニングに有用である事を示唆している。今後、PTXによるMfn2発現量低下と神経障害との関係と明らかにすることで、新たな治療・予防法の確立につながると考えれられる。