@entity42748 protects sympathetic neurons from apoptosis caused by nerve growth factor (NGF) deprivation. Here, we report for the first time that @entity2367 generated "de novo" is also anti-apoptotic. Moreover, @entity42748 is converted to long-chain @entity9932 in a process inhibited by @entity18639 . The anti-apoptotic effect of @entity42748 is due to the short analogue as to the long-chain @entity9932 . @entity42748 shares mechanisms of action with NGF. @entity42748 induces TrkA phosphorylation and selective activation of the @entity4357 3-kinase (PI3-kinase)/ @entity2308 pathway but not the MAPK/ERK pathway. Importantly, the PI3-kinase inhibitor @entity2306 abolishes the pro-survival effect of @entity42748 . We identified a novel way to activate retrograde-mediated neuronal survival in the absence of NGF. Using compartmented cultures we show that addition of @entity42748 exclusively to distal axons is sufficient to abort nuclear apoptosis. Our system offers a very unique alternative to understand the molecular bases of retrograde signaling in the absence of retrograde transport of neurotrophins. In search for a natural ligand that leads to @entity2367 generation we examined the activation of the @entity4291 (SM) cycle downstream the @entity11451 ( @entity11451 ). We found that in sympathetic neurons, selective activation of @entity11451 by brain-derived neurotrophin factor or NGF plus K252a induces elevation of @entity2367 that correlates with SM hydrolysis. However, @entity11451 activation does not generate sufficient @entity2367 to block apoptosis probably due to the rapid decrease in @entity11451 expression that occurs upon NGF withdrawal.

Inhibition of rat sympathetic neuron apoptosis by @entity2367 . Role of @entity11451 in XXXX generation.

@entity42748 :: ('MESH:C101954', 'Chemical') :: ['C6-ceramide'] @entity2308 :: ('24185(Tax:10116)', 'Gene') :: ['Akt'] @entity18639 :: ('MESH:C056933', 'Chemical') :: ['fumonisin B1'] @entity4291 :: ('CHEBI:17636', 'Chemical') :: ['sphingomyelin'] @entity2306 :: ('MESH:C085911', 'Chemical') :: ['LY294002'] @entity2367 :: ('CHEBI:17761', 'Chemical') :: ['ceramide'] @entity11451 :: ('24596(Tax:10116)', 'Gene') :: ['p75 neurotrophin receptor', 'p75NTR'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidyl inositol'] @entity9932 :: ('MESH:D002518', 'Chemical') :: ['ceramides']
@entity2367 :: (CHEBI:17761,Chemical) :: ['ceramide']
