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受体酪氨酸激酶与酪氨酸激酶抑制剂:多发性硬化症治疗成功的新希望

Receptor Tyrosine Kinase and Tyrosine Kinase Inhibitors: New Hope for Success in Multiple Sclerosis Therapy.

作者信息

Mirshafiey Abbas, Ghalamfarsa Ghasem, Asghari Babak, Azizi Gholamreza

机构信息

Dr. Mirshafiey is from the Departmant of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Dr. Ghalamfarsa is from Cellular & Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran; Dr. Asghari is from Antimicrobial Resistance Research Center, Faculty of Medicine, Iran University of Medical Science, Tehran, Iran; Dr. Azizi is from Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran.

出版信息

Innov Clin Neurosci. 2014 Jul;11(7-8):23-36.

Abstract

Receptor tyrosine kinases (RTKs) are essential components of signal transduction pathways that mediate cell-to-cell communication and their function as relay points for signaling pathways. They have a key role in numerous processes that control cellular proliferation and differentiation, regulate cell growth and cellular metabolism, and promote cell survival and apoptosis. Recently, the role of RTKs including TCR, FLT-3, c-Kit, c-Fms, PDGFR, ephrin, neurotrophin receptor, and TAM receptor in autoimmune disorder, especially rheumatoid arthritis and multiple sclerosis has been suggested. In multiple sclerosis pathogenesis, RTKs and their tyrosine kinase enzymes are selective important targets for tyrosine kinase inhibitor (TKI) agents. TKIs, compete with the ATP binding site of the catalytic domain of several tyrosine kinases, and act as small molecules that have a favorable safety profile in disease treatment. Up to now, the efficacy of TKIs in numerous animal models of MS has been demonstrated, but application of these drugs in human diseases should be tested in future clinical trials.

摘要

受体酪氨酸激酶(RTKs)是信号转导通路的重要组成部分,介导细胞间通讯,并作为信号通路的中继点发挥作用。它们在控制细胞增殖和分化、调节细胞生长和细胞代谢以及促进细胞存活和凋亡的众多过程中起着关键作用。最近,有人提出包括TCR、FLT-3、c-Kit、c-Fms、PDGFR、ephrin、神经营养因子受体和TAM受体在内的RTKs在自身免疫性疾病,尤其是类风湿性关节炎和多发性硬化症中的作用。在多发性硬化症发病机制中,RTKs及其酪氨酸激酶酶是酪氨酸激酶抑制剂(TKI)药物的选择性重要靶点。TKI与几种酪氨酸激酶催化域的ATP结合位点竞争,并作为在疾病治疗中具有良好安全性的小分子发挥作用。到目前为止,TKI在多种MS动物模型中的疗效已得到证实,但这些药物在人类疾病中的应用应在未来的临床试验中进行测试。

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