Neutral Glycosphingolipids As Neuroinflammatory Signaling Molecules In Neurodegeneration

Abstract

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 autoantibodies 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.

Sphingolipid abnormalities in encephalomyeloradiculoneuropathy (EMRN) are associated with an anti‐neutral glycolipid antibody

“…On the other hand, the complement pathway is an important player in innate immune responses and it consists of three different activating pathways, all of which converge with the activation of complement C5, yielding the C5a active fragment and finally leading to the formation of membrane attack complex [ 10 ]. Intriguingly, previous studies have shown that the production of anti‐neutral glycolipid (NGL) autoantibody (which leads to the activation complement system) has been observed in experimental and human Gaucher disease (GD) and amyotrophic lateral sclerosis (ALS) transgenic mice ([ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], see [ 14 ] for review).…”