Neutral glycosphingolipids as neuroinflammatory signaling molecules in neurodegeneration

Previous studies have shown that various glycolipids including neutral and acidic glycosphingolipids (GSLs) involve multiple biological events such as survival, neuronal development and differentiation processes. Moreover, recent reports have indicated that some neutral GSLs are involved in neuroinflammatory signaling and therefore involved in the occurrence of certain neurological diseases. Sphingolipids, cholesterol, and glycerophospholipids are essential constituents of neuronal membranes which function as a protective barrier of neuronal cells against the external environment and providing essential biochemical platform for proper neuronal actions and functions. At present, however, detailed molecular basis of how GSLs transmit the signals in neuroinflammatory reactions in vivo remains to be elucidated. Furthermore, we recently identified new type of autoantibodies against neutral GSLs, especially lactosylceramide in a neuroinflammatory disorder, encephalomyeloradiculoneuropathy (EMRN) and found these autoan-tibodies can be used as a surrogate marker for this disorder. These anti-neutral glycolipids antibodies strongly indicate that they can be a strong inducer for neuroinflammation of the brain and peripheral nervous system as well by involving innate immunity. In this review, I focused the biological and immunological activities and implications of GSLs and their autoantibodies, especially in terms of neuroinflammatory reactions in animals and human.