Lipids and synaptic functions

Synaptic functions have long been thought to be driven by proteins, especially the SNARE complex, contrasting with a relatively passive role for lipids constituting cell membranes. It is now clear that not only lipids, i.e. glycerophospholipids, sphingolipids and sterols, play a determinant role in the dynamics of synaptic membranes but they also actively contribute to the endocytosis and exocytosis of synaptic vesicles in conjunction with synaptic proteins. On the other hand, a growing number of inborn errors of metabolism affecting the nervous system have been related to defects in the synthesis and remodelling of fatty acids, phospholipids and sphingolipids. Alterations of the metabolism of these lipids would be expected to affect the dynamics of synaptic membranes and synaptic vesicles. Still, only few examples are currently documented. It remains to be determined to which extent the pathophysiology of disorders of complex lipids biosynthesis and remodelling share common pathogenic mechanisms with the more traditional synaptopathies.