Sphingolipids as therapeutics.

The sphingolipid field has made significant strides over the past 10 years: from identifying metabolites of the sphingomyelin pathway as second messengers to discerning the molecular biology and biophysics of these lipid-derived second messengers. Building upon this vast basic science literature, scientists from multiple disciplines have begun to translate manipulations of endogenous sphingolipid metabolites and targets into therapeutic initiatives. Multiple publications have reviewed the biochemistry [Biochemistry 40 (16) (2001) 4893 [1]; Environ. Health Perspect. 109 (Suppl. 2) (2001) 283 ], biophysics [J. Cell Physiol. 184 (3) (2000) 285; Trends Cell Biol. 10 (10) (2000) 408 ], molecular biology [Biochim. Biophys. Acta 1426 (2) (1999) 347 ], and physiology [J. Biol. Chem. 277 (29) (2002) 25851; J. Biol. Chem. 277 (29) (2002) 25847 ] of sphingolipid metabolites. The present review serves to document the emerging concept of sphingolipid metabolites as therapeutics with clear clinical potential.