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凋亡信号调节激酶-1抑制剂在非酒精性脂肪性肝炎中的研究进展

韩磊, 张小猛, 全旭, 雷永华, 钱海

韩磊, 张小猛, 全旭, 雷永华, 钱海. 凋亡信号调节激酶-1抑制剂在非酒精性脂肪性肝炎中的研究进展[J]. 中国药科大学学报, 2019, 50(2): 135-142. DOI: 10.11665/j.issn.1000-5048.20190202
引用本文: 韩磊, 张小猛, 全旭, 雷永华, 钱海. 凋亡信号调节激酶-1抑制剂在非酒精性脂肪性肝炎中的研究进展[J]. 中国药科大学学报, 2019, 50(2): 135-142. DOI: 10.11665/j.issn.1000-5048.20190202
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HAN Lei, ZHANG Xiaomeng, QUAN Xu, LEI Yonghua, QIAN Hai. Research progress of apoptosis signal regulating kinases-1 and its inhibitors in non-alcoholic steatohepatitis[J]. Journal of China Pharmaceutical University, 2019, 50(2): 135-142. DOI: 10.11665/j.issn.1000-5048.20190202
Citation: HAN Lei, ZHANG Xiaomeng, QUAN Xu, LEI Yonghua, QIAN Hai. Research progress of apoptosis signal regulating kinases-1 and its inhibitors in non-alcoholic steatohepatitis[J]. Journal of China Pharmaceutical University, 2019, 50(2): 135-142. DOI: 10.11665/j.issn.1000-5048.20190202
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凋亡信号调节激酶-1抑制剂在非酒精性脂肪性肝炎中的研究进展

  • 1.

    中国药科大学新药研究中心

  • 2.

    南京圣和药业股份有限公司

基金项目: 国家自然科学基金资助项目(No.81673299)

Research progress of apoptosis signal regulating kinases-1 and its inhibitors in non-alcoholic steatohepatitis

摘要

    摘要
  • 摘要: 非酒精性脂肪性肝炎(non-alcoholic steatohepatitis，NASH)是最常见的慢性肝病，当前未见有效疗法。凋亡信号调节激酶-1(apoptosis signal regulating kinases 1，ASK-1)是细胞丝裂原活化蛋白激酶激酶激酶(mitogen-activated protein kinase kinase kinases，MAPKKKs)家族成员之一，当机体受到细胞内活性氧簇应激、内质网应激、钙内流和细胞外炎症等信号刺激时，ASK-1激活c-Jun氨基末端激酶(c-Jun amino terminal kinasec，JNK)和p38 MAPK通路，从而促进细胞增殖、分化、凋亡以及炎症因子的产生，诱发NASH、纤维化等疾病，因此可通过抑制ASK-1的活性来治疗NASH。本文对当前NASH的治疗手段、ASK-1结构和作用机制以及近年ASK-1抑制剂治疗NASH的研究进展进行综述，旨在为该类抑制剂的设计与开发提供参考。
    Abstract: Non-alcoholic steatohepatitis(NASH)is the most common chronic liver disease. However, the treatment of NASH remains challenging. Apoptosis signal regulating kinases-1(ASK-1)is a member of mitogen-activated protein kinase kinase kinases(MAPKKKs). When the body is stimulated by reactive oxygen species, endoplasmic reticulum stress, calcium influx and extracellular inflammatory signals, c-Jun amino terminal kinases(JNK)and p38 MAPK wiube activated, which then promotes cell proliferation, differentiation, apoptosis and production of inflammatory factors, and causes NASH, fibrosis and other diseases. Therefore, ASK-1 inhibitors can be used to treat NASH. This paper reviews the current treatment methods of NASH, the structure and mechanism of ASK-1, and the research progress of ASK-1 inhibitors in the treatment of NASH in recent years, which aims to explore the guiding significance for the design and development of ASK-1 inhibitors.
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  • 刊出日期:  2019-04-24

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