How do different cell populations orchestrate myelin regeneration?

Approximately 35 in 100,000 people are affected by diseases associated with loss of myelin, generally described as demyelinating diseases. Demyelinating diseases encompass many different pathological conditions characterized by heterogeneous and sometimes disease-specific etiopathological mechanisms. While several approaches aimed at ameliorating the symptoms and the progression of some of these diseases exist, the most effective cure for all demyelinating diseases would be regeneration of lost myelin. Myelin regeneration occurs spontaneously in the central nervous system in response to myelin damage but is inefficient for a variety of reasons, especially in human patients. In this review, we will discuss the contributions of different cell populations to the creation of conditions permissive for effective remyelination and to the formation of new myelin after injury. Moreover, we would like to highlight the importance of sphingolipids in the network of interactions between these cell populations. Mutations in genes encoding sphingolipid metabolic enzymes (such as GALC) represent a major risk factor for multiple sclerosis, and alterations in sphingolipid metabolism in specific cell types contribute to myelin damage. On the other hand, sphingolipid signaling, in particular through sphingosine 1 phosphate, directly affects the process of myelin regeneration, with distinct effects on different cellular populations.