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蛋白激酶在小胶质细胞介导的神经炎症中的新作用。

Emerging roles of protein kinases in microglia-mediated neuroinflammation.

作者信息

Lee Sun-Hwa, Suk Kyoungho

机构信息

New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.

Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.

出版信息

Biochem Pharmacol. 2017 Dec 15;146:1-9. doi: 10.1016/j.bcp.2017.06.137. Epub 2017 Jul 4.

Abstract

Neuroinflammation is mediated by resident central nervous system glia, neurons, peripherally derived immune cells, blood-brain barrier, and inflammatory mediators secreted from these cells. Neuroinflammation has been implicated in stroke and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Protein kinases have been one of the most exploited therapeutic targets in the current pharmacological research, especially in studies on cancer and inflammation. To date, 32 small-molecule protein kinase inhibitors have been approved by the United States Food and Drug Administration for the treatment of cancer and inflammation. However, there is no drug effectively targeting neuroinflammation and/or neurodegenerative diseases. Recent studies have advanced several protein kinases as important drug targets in neuroinflammation and/or neurodegenerative diseases. Here, we review emerging protein kinases potentially involved in neuroinflammation and subsequent neurodegenerative diseases.

摘要

神经炎症由中枢神经系统的常驻胶质细胞、神经元、外周来源的免疫细胞、血脑屏障以及这些细胞分泌的炎症介质介导。神经炎症与中风和神经退行性疾病有关,如阿尔茨海默病、帕金森病、多发性硬化症和肌萎缩侧索硬化症。蛋白激酶一直是当前药理学研究中最受关注的治疗靶点之一,尤其是在癌症和炎症研究中。迄今为止,已有32种小分子蛋白激酶抑制剂被美国食品药品监督管理局批准用于治疗癌症和炎症。然而,尚无有效靶向神经炎症和/或神经退行性疾病的药物。最近的研究提出了几种蛋白激酶作为神经炎症和/或神经退行性疾病的重要药物靶点。在此,我们综述了可能参与神经炎症及后续神经退行性疾病的新兴蛋白激酶。

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