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机构地区:[1]第二军医大学药学院微生物与生化药学教研室,上海200433 [2]福建中医药大学药学院,福建福州350108
出 处:《药学实践杂志》2015年第5期392-395,共4页Journal of Pharmaceutical Practice
基 金:国家自然科学基金(30500093);国家科技部"重大新药创制"专项(2009ZX09103-690);上海市科委重点项目(04JC14002);军队"十一五"计划(06Q042);上海市高校优秀青年教师科研专项基金(ejd09011)
摘 要:肿瘤坏死因子(TNF)信号通路是很有价值的治疗靶标,抗TNF药物已成功治疗自身免疫和炎症疾病,但传统的抗TNF药物完全封闭TNF信号通路,导致影响自身的免疫调节和监视功能而增加感染、致癌的风险和产生新的自身免疫疾病。选择性抑制sTNF/TNFR1而保留mTNF/TNFR2传导的信号能减少副作用而不降低治疗效果。该文探讨了选择性抑制TNFR1介导的信号通路对治疗TNF相关疾病的意义,分析TNF识别并激活肿瘤坏死因子受体(TNFR)的作用机制,可能会为设计新药提供新的思路。TNF signaling pathway was a valuable target ,and anti-TNF drugs were successfully used to treat autoim-mune and inflammatory diseases .But this therapy abrogate some beneficial TNF signaling ,leading to increased risk of infection and malignancy ,and the onset of new auto-immune diseases .Inhibiting the soluble TNF/TNFR1 axis while saving the benefi-cial transmembrane TNF/TNFR2 signaling untouched was a new approach .Because it inhibited the pathological effects of TNF and reduced the side effects ,and opened the way for the treatment of other diseases in which TNFR2 inhibition was detrimen-tal .The significance of the selective inhibition of TNFR1-mediated signaling pathways for TNF-related diseases was discussed and the mechanism of TNF identification TNFR was clarified ,which might provide new ideas for the design of new drugs .
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