Targeting the sphingosine kinase/sphingosine 1-phosphate pathway in disease: review of sphingosine kinase inhibitors.
Targeting the sphingosine kinase/sphingosine 1-phosphate pathway in disease: review of sphingosine kinase inhibitors.
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DOI：
10.1016/j.bbalip.2012.07.002
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Obeid LM
中科院分区：
文献类型：
--
作者：
Orr Gandy KA;Obeid LM
1-磷酸鞘氨醇（S1 P）是一种重要的具有生物活性的鞘脂代谢产物，参与许多生理和细胞过程。S1 P不仅通过定义质膜的组分在细胞中发挥结构性作用，而且在过去的20年中，它已涉及各种重要的细胞信号传导途径和生理过程：例如细胞迁移、存活和增殖、细胞结构、细胞-细胞接触和粘附、血管发育、动脉粥样硬化、急性肺损伤和呼吸窘迫，炎症和免疫以及肿瘤发生和转移。考虑到S1 P参与的细胞和生理过程的广泛多样性，很明显，为什么控制S1 P合成和降解的机制以及这些过程的调节方式是必要的。随着对鞘氨醇激酶（SK）/S1 P通路调控的深入了解，许多潜在的治疗靶点可能被揭示出来。本文综述了SK/S1 P通路在疾病中的作用，总结了现有的SK酶抑制剂，并探讨了其作为治疗药物的潜力。
Sphingosine 1-phosphate (S1P) is an important bioactive sphingolipid metabolite that has been implicated in numerous physiological and cellular processes. Not only does S1P play a structural role in cells by defining the components of the plasma membrane, but in the last 20 years it has been implicated in various significant cell signaling pathways and physiological processes: for example, cell migration, survival and proliferation, cellular architecture, cell-cell contacts and adhesions, vascular development, atherosclerosis, acute pulmonary injury and respiratory distress, inflammation and immunity, and tumorogenesis and metastasis. Given the wide variety of cellular and physiological processes in which S1P is involved, it is immediately obvious why the mechanisms governing S1P synthesis and degradation, and the manner in which these processes are regulated, are necessary to understand. In gaining more knowledge about regulation of the Sphingosine Kinase (SK)/S1P pathway, many potential therapeutic targets may be revealed. This review explores the roles of the SK/S1P pathway in disease, summarizes available SK enzyme inhibitors and examines their potential as therapeutic agents.
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