Discovery of a new brain enzyme, galactocerebroside sulfate sulfatase, which catabolizes sulfatide at a neutral pH has been accomplished. We have found a microsome associated inhibitor of the neutral sulfatidase. The significance of this observation in relation to AIDS is that sulfatides have now been unequivocally shown to bind HIV in neuronal and other cells. Our ability to regulate brain sulfatide metabolism may have relevance to the replication of HIV in neuronal tissues. Since sulfatides are an important component of myelin, this enzyme may have a role in myelination, remyelination and because of its activity at neutral pH it could be involved in cell signaling, possibly in a """"""""sulfatide cycle"""""""" in Schwann cells and in oligodendrocytes. GP120 has been shown to bind to sulfatides; the effect of GP120 binding on N-sulfatide activity will be examined and correlated with increases in cytosolic ca2+ and mRNA for TNFa and IL8. We will continue our work on the neutral sulfatidase to determine the characteristics of the enzyme, its location in the cell and whether we can regulate its activity in vivo in a Schwann cell line by use of this inhibitor. This inhibitor will also be characterized.
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