2020年
シュワン細胞の分化促進を基軸としたタキサン系抗がん剤誘発末梢神経障害の根本的治療法の探索
日本薬理学会年会要旨集
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- 巻
- 93
- 号
- 0
- 開始ページ
- 1
- 終了ページ
- SS-37
- 記述言語
- 日本語
- 掲載種別
- DOI
- 10.1254/jpssuppl.93.0_1-SS-37
- 出版者・発行元
- 公益社団法人 日本薬理学会
<p>We have previously demonstrated that paclitaxel reduces myelin-forming Schwann cells due to dedifferentiation of mature Schwann cells, prior to the induction of cytotoxicity against peripheral neurons. This cytotoxic process should be a causative pathogenesis of taxane-related chemotherapy-induced peripheral neuropathy (CIPN). To find the causal treatment of CIPN, we screened approved drugs with the ability to promote Schwann cell differentiation. Among numerous medicines,the most effective compounds identified was a PDE inhibitor, which promoted differentiation of immature Schwann cells, as indicated by increased expression of a mature Schwann cell marker, MBP. In a mixed culture of Schwann cells and DRG neurons, the co-treatment with a PDE inhibitor (30 mM) significantly suppressed paclitaxel (10</p><p>nM)-induced loss of myelin-forming Schwann cells (i.e. demyelination). In addition, the long-term administration of a PDE inhibitor (0.3% in chow diets) during the paclitaxel injection-period, paclitaxel (5 mg/kg, i.p.) twice a week for 8 weeks, reduced mechanical hypersensitivity in mice. Thus, we propose here that a PDE inhibitor, which prevents paclitaxel-induced Schwann cell dedifferentiation and demyelination, can be a therapeutic candidate to suppress paclitaxel-related CIPN.</p>
- リンク情報
- ID情報
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- DOI : 10.1254/jpssuppl.93.0_1-SS-37
- CiNii Articles ID : 130007811421