Premium
Lactosylceramide: a lipid second messenger in neuroinflammatory disease
Author(s) -
Won JeSeong,
Singh Avtar K.,
Singh Inderjit
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04822.x
Subject(s) - lactosylceramide , signal transduction , microbiology and biotechnology , chemokine , proinflammatory cytokine , protein kinase a , autocrine signalling , biology , lipid signaling , nitric oxide synthase , kinase , microglia , inflammation , biochemistry , immunology , receptor , enzyme
Inflammatory disease plays a critical role in the pathogenesis of many neurological disorders. Astrogliosis and induction of pro‐inflammatory mediators such as chemokines, cytokines and inducible nitric oxide synthase (iNOS) are the ‘hallmarks’ of inflammatory disease. Increased activity of lactosylceramide (LacCer) synthase and increased synthesis of LacCer during glial proliferation, and induction of pro‐inflammatory cytokines and iNOS suggests a role for LacCer in these cellular signaling pathways. Studies using complementary techniques of inhibitors and antisense reported that inhibition of LacCer synthesis inhibits glial proliferation, as well as the induction of pro‐inflammatory mediators (cytokines and iNOS). This inhibition was bypassed by exogenous LacCer, but not by other related lipids (e.g. glucosylceramide, galactocerebroside, GD1, GM1), indicating a role for LacCer in inflammatory signaling pathways. Furthermore, inhibition of glial proliferation and induction of inflammatory mediators by antisense to Ras GTPase, PI3Kinase and inhibitors of mitogen‐activated protein kinase indicate the participation of the phosphoinositide 3‐kinase (PI3Kinas)/Ras/mitogen‐activated protein kinase/nuclear factor‐κB (NF‐κB) signaling pathways in LacCer‐mediated inflammatory events thus exposing additional targets for therapeutics for inflammatory disease conditions.