Lipid rafts and neurological diseases

The different populations of brain cells are characterised by evident membrane polarisation with the creation of distinct morphological and functional subcompartments, whose formation, stabilisation and functions require sophisticated geometric features and a high level of lateral order, which are, at least in part, driven by the collective properties of membrane lipids. Lipid‐driven membrane organisation allows the segregation of membrane‐associated components into specific ‘lipid membrane domains’ or lipid rafts, which function as dynamic platforms for signal transduction, protein processing and membrane turnover. From this point of view, sphingolipids (SLs), polar membrane lipids present as minor components in all eukaryotic cell membranes but highly enriched in neuron and myelin membranes, play crucial roles. In fact, the metabolism of SLs is precisely regulated along the differentiation and development of neurons and oligodendrocytes, leading to the expression of peculiar cell‐specific SL patterns essential for the maintenance of the functional integrity of the nervous system, while, on the other hand, alterations in SL homeostasis, which lead to abnormal lipid raft organisation and consequent deregulation of lipid raft‐dependent events, are a common trait in diverse major brain diseases.