以結構為導向繪製耳毒性相關蛋白質圖譜：藥物進入、損傷放大、細胞死亡執行與內源性耳保護

// Structure-guided mapping of ototoxicity-related proteins: drug entry, damage amplification, cell death execution, and endogenous otoprotection

綜述將耳毒性蛋白分四層：進入、擴增、執行與保護｜列出關鍵通路如TMC1/TMC2（聲毛細胞通道）、OCT2、CTR1與NOX3｜結論：耳保護需精準多靶調控，並兼顧藥物可行性、遞送與時機，指導臨床應用

// This review organizes proteins involved in drug-induced ototoxicity into four functional layers—drug access/entry, intracellular damage amplification, cell death execution, and endogenous protective/repair responses—to guide rational otoprotective strategies. Through a structure-guided analysis of protein function, available structures, ligands, binding sites, and tractability, it highlights key entry checkpoints (e.g., TMC1/TMC2, OCT2, CTR1, TRPV1), damage amplifiers (e.g., NOX3, inflammatory mediators, RGS17, PRMTs, CDK2), execution mediators (e.g., Bax, calpains, caspases), and protective systems (e.g., HSPs, G6PD, BDNF, PINK1, KCNQ4, sirtuins). The authors conclude that effective otoprotection will require precise modulation of multiple targets rather than simple inhibition, and must account for druggability, delivery, timing, model limitations, and target prioritization.

Published 2026年9月26日