An unraveled mystery: What's the role of brain sphingolipids in neurodegenerative and psychiatric disorders

Sphingolipids are a class of lipids highly expressed in brain, especially in the myelin sheath of white matter. In recent years, with the development of lipidomics, the role of brain sphingolipids in neurological disorders have raised lots of interests due to their function in neuronal signal transduction and survival. Although not thoroughly investigated, some previous studies have indicated that sphingolipids homeostasis are closely linked to the etiology and development of some neurological disorders. For example, disrupted sphingolipids level have been found in clinic patients with neurological disorders, such as neurodegeneration and psychiatric disorders. Conversely, intervention of sphingolipids metabolism by modulating activity of related enzymes also could result in pathological deficits identified in neurological disorders. Moreover, the alteration of sphingolipids catabolic pathway in the brain could be partly represented in cerebrospinal fluid and blood tissues, which show diagnostic potential for neurological disorders. Therefore, our review aims to summarize and discuss the known contents of bioactive sphingolipid metabolism with their related studies in neurodegenerative and psychiatric disorders, to help understand the potential mechanism underlying sphingolipid regulation of neural function and provide possible directions for further study. The new perspectives in this promising field will open up new therapeutic options for neurological disorders.