Study on mechanisms of inflammation in the central nervous system of gangliosidosis

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Sandhoff disease is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase and strage of GM2 gangliodside and related glycolipid. Recently we and others have reported several immunological abnormalities in the CNS.However, little is known about the mechanism underlying the action of accumulation Gmix as a leading cause for pathological inflammatory responses in the brain. Here we reported that autoantibodies and released-Gmix from apoptotic neuronal cells mediate the nervous inflammation in microglia and astorocytes. The Gmix storage of neuronal cells in SD mice can lead to the release of Gmix from Apoptotic neuronal cells into the extracellular space. The exposure to Gmix can induce the production of TNF-alpha, IL-6 and MIP-1alpha via the Toll-like receptor 4 in the SD mice microglia and astorocytes.Taken together, these results suggest that autoantibodies and released-Gmix may provide to cause nervous inflammatory condition in the brain of SD mice.