CERAMIDE/SPHINGOSINE-1-PHOSPHATE IN CELLS SURVIVAL AND DEATH: IMPLICATION IN ALZHEIMER'S DISEASE

Ceramide and sphingosine-1-phosphate (S1P) are very active sphingo-lipid messengers which play a crucial role in regulation of neuronal cells survival and death. Alternation of ceramide/S1P rheostat is related to several pathological disorders including Alzheimer's disease. Ceramides are involved in cells proliferation, differentiation and apoptotic death, while S1P enhances cell proliferation and antagonizes apoptosis. S1P regulates cellular processes by binding to five specific G protein coupled-receptors (S1PRI-5). The aim of the study was to investigate the molecular processes of neuronal death evoked by ceramide and the role of S1P in neuroprotection. Our study indicated that ceramide enhanced significantly the level of free radicals and decreased neuronal cells (SHSY5Y) viability through inhibition of PI3-K/Akt pathway. Ceramide also decreased anti-apoptotic (Bcl-2) and increased pro-apoptotic (Bax, Hrk) gene expression. Exogenously added S1P increased the viability of cells through S1PR (1-3) receptors-dependent mechanism. S1P also increased Bcl-2 gene expression and decreased the gene expression of Hrk protein. Summarizing, our study indicated that the action of ceramide and S1P on mitochondria may control neuronal fate and may play a crucial role in neurodegeneration and neuroprotection.