Lyase to live by: sphingosine phosphate lyase as a therapeutic target.
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
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.


CONCLUSIONS
This review provides evidence that SPL is a potential target for pharmacological manipulation for the treatment of malignant, autoimmune, inflammatory and other diseases.
Kumar
Ashok
A
Children's Hospital Oakland Research Institute (CHORI), Oakland, CA 94609-1673, USA.
Saba
Julie D
JD
D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000201:enzymology; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D000446:Aldehyde-Lyases; C022649:sphingosine 1-phosphate lyase (aldolase)