The riddle of sphingolipid structure-function relationship in the nervous system

Sphingolipids are ubiquitous in the membranes of nervous system cells. They constitute about 20% of brain lipids. Perturbations of their metabolism result in dysregulation of nervous system homeostasis leading to pathologies. The structural characteristics of sphingolipid precursors, the long-chain bases, and ceramides, determine their biophysical properties and functions, as well as those of complex sphingolipids. In the current review, we are focusing on the role of chain length, saturation, and hydroxylation of sphingolipid precursors in nervous system physiology and pathology. We discuss the enzymes from the sphingolipid metabolic pathway catalyzing the reactions introducing the structural changes in the long chain bases and ceramides. We also focus on a recently discovered class of atypical neurotoxic sphingolipids as intermediates in peripheral neuropathies.