BioCentury
ARTICLE | Targets & Mechanisms

Depressing sphingolipids

July 18, 2013 7:00 AM UTC

European researchers have obtained the most compelling evidence yet that targeting sphingolipid metabolism could help treat depression.1 The team has shown that two known antidepressants inhibit sphingolipid metabolism and now is planning to screen for other inhibitors that also elicit antidepressive effects.

Previous work has shown that some serotonin-specific reuptake inhibitor (SSRI) antidepressants have an inhibitory effect on a key lipid processing enzyme called sphingomyelin phosphodiesterase 1 acid lysosomal (SMPD1; ASM).2 SMPD1 is a membrane protein facing the lysosomal lumen that converts sphingomyelin into ceramide(see "Hitting ceramide for depression"). Ceramide diffuses out of the lysosome to other cellular membranes to modulate signaling pathways involved in cell growth, inflammation and intracellular responses to bacterial infection...