Cellular Signaling By Sphingosine And Sphingosine 1-phosphate. Their Opposing Roles In Apoptosis.
Published 2002 · Medicine, Chemistry
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S1P is involved in a variety of physiological and pathophysiological processes that involve proliferation and migration (Pyne and Pyne, 2000). These include tumor invasion, angiogenesis, atherosclerosis and differentiation. Anti-cancer therapies could include the use of EDG receptor sub-type-specific antagonists or EDG receptor knockout. The inhibition of SPHK is also a promising approach. For instance, DMS has been used to induce apoptosis of solid tumors (Park et al. 1994; Sakakura et al., 1997). Novel SPHK inhibitors with higher potency (De Jonge et al., 1999) are also being developed which may have improved clinical efficacy. Conversely, activation of SPHK or inhibition of S1P phosphatase and S1P lyase could be used to protect against apoptosis. This may be of particular relevance to neurological disorders, such as Alzheimer’s and Parkinson’s disease, which are associated with de-regulated apoptosis.
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