依赖裂合酶生存：神经酰胺磷酸裂合酶作为治疗靶点。
Lyase to live by: sphingosine phosphate lyase as a therapeutic target.
机构信息
Children's Hospital Oakland Research Institute (CHORI), Oakland, CA 94609-1673, USA.
出版信息
Expert Opin Ther Targets. 2009 Aug;13(8):1013-25. doi: 10.1517/14728220903039722.
BACKGROUND
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.
OBJECTIVE/METHODS: This review summarizes the current know-ledge of SPL structure, function and regulation, its involvement in various disease states and currently available small molecules known to modulate SPL activity.
RESULTS/CONCLUSION: This review provides evidence that SPL is a potential target for pharmacological manipulation for the treatment of malignant, autoimmune, inflammatory and other diseases.
背景
鞘氨醇 1-磷酸（S1P）是一种具有生物活性的脂质，可调节细胞增殖、存活和迁移，在血管生成和淋巴细胞迁移中发挥重要作用。循环和组织中的 S1P 水平受到严格调节，以维持细胞的正常功能，而该系统的失调可能导致某些人类疾病的病理生理学变化。鞘氨醇磷酸裂解酶（SPL）可不可逆地降解 S1P，因此通过调节细胞内 S1P 水平以及淋巴器官和循环血液和淋巴之间存在的化学 S1P 梯度，充当调节 S1P 信号的守门员。然而，SPL 也会产生可能与人类疾病相关的生化产物。SPL 直接参与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。
目的/方法：本综述总结了 SPL 的结构、功能和调节的最新知识，以及其在各种疾病状态中的作用和目前已知可调节 SPL 活性的小分子。
结果/结论：本综述提供的证据表明，SPL 是一种潜在的药物靶点，可用于治疗恶性、自身免疫、炎症等疾病。
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