Lyase to live by: sphingosine phosphate lyase as a therapeutic target.
Lyase to live by: sphingosine phosphate lyase as a therapeutic target.
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DOI：
10.1517/14728220903039722
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发表时间：
2009-08
影响因子：
5.8
通讯作者：
Saba JD
中科院分区：
文献类型：
--
作者：
Kumar A;Saba JD
1-磷酸鞘氨醇 (S1P) 是一种生物活性脂质，可调节细胞增殖、存活和迁移，在血管生成和淋巴细胞运输中发挥重要作用。循环和组织中的 S1P 水平受到严格调节，以保证细胞的正常功能，该系统的失调可能会导致某些人类疾病的病理生理学。磷酸鞘氨醇裂解酶 (SPL) 不可逆地降解 S1P，从而充当守门人，通过调节细胞内 S1P 水平以及淋巴器官与循环血液和淋巴液之间存在的化学 S1P 梯度来调节 S1P 信号传导。然而，SPL 还产生可能与人类疾病相关的生化产品。 SPL 直接涉及各种生理和病理过程，包括细胞应激反应、癌症、免疫、造血功能、肌肉稳态、炎症和发育。本综述将总结目前对 SPL 结构、功能、调节、其与各种疾病状态的参与以及目前已知的调节 SPL 活性的小分子的了解。本综述提供的证据表明，SPL 本身是治疗恶性、自身免疫、炎症和其他疾病的药物操作的潜在靶点。
Sphingosine 1-phosphate (S1P) is a bioactive lipid that regulates cell proliferation, survival and migration and plays an essential role in angiogenesis and lymphocyte trafficking. S1P levels in the circulation and tissues are tightly regulated for proper cell functioning, and dysregulation of this system may contribute to the pathophysiology of certain human diseases. Sphingosine phosphate lyase (SPL) irreversibly degrades S1P and thereby acts as a gatekeeper that regulates S1P signaling by modulating intracellular S1P levels and the chemical S1P gradient that exists between lymphoid organs and circulating blood and lymph. However, SPL also generates biochemical products that may be relevant in human disease. SPL has been directly implicated in various physiological and pathological processes, including cell stress responses, cancer, immunity, hematopoietic function, muscle homeostasis, inflammation and development. This review will summarize the current knowledge of SPL structure, function, regulation, its involvement in various disease states, and currently available small molecules known to modulate SPL activity. This review provides he evidence that SPL presents itself as a potential target for pharmacological manipulation for the treatment of malignant, autoimmune, inflammatory and other diseases.
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