Crosstalk between sphingolipids and vitamin D3: potential role in the nervous system

Sphingolipids are both structural and bioactive compounds. In particular ceramide and sphingosine 1-phosphate regulate cell fate, inflammation, and excitability. 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), is known to play an important physiological role on growth and differentiation in a variety of cell types, including neural cells, through genomic actions, mediated by its specific receptor, and non-genomic actions resulting in the activation of specific signalling pathways. 1,25(OH)2D3 and sphingolipids, in particular sphingosine-1-phosphate, share many common effectors, including calcium regulation, growth factors and inflammatory cytokines, but whether they could act synergistically is still unknown. Alterations in the signalling and content of sphingolipids and 1,25(OH)2D3 have been found in neurodegenerative diseases and fingolimod, a structural analogue of sphingosine, has been approved for the treatment of multiple sclerosis. This review, after a brief description of the role of sphingolipids and 1,25(OH)2D3, will focus on the potential crosstalk of sphingolipids and 1,25(OH)2D3 in neural cells.