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Neuroscience Seminar: Norman J. Haughey, Ph.D., The Johns Hopkins University School of Medicine

Targeting neutral sphingomyelinase to improve remyelination


Norman J. Haughey
Ph.D. Professor and Vice Chair of Research for the Department of Neurology
Professor of Neuroimmunology and Neurological Infections
Johns Hopkins University School of Medicine


For reasons that are not completely understood, remyelination is often incomplete, resulting in thin myelin sheaths with a disorganized myelin structure.  We found that the disorganized structure of regenerated myelin sheaths involves a modification in the composition of myelin lipids with increased ceramide and sphingomyelin content, and reduced sulfatide. We investigated the cellular basis for this altered myelin structure, and found that induced expression of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) during the differentiation of oligodendrocyte progenitor cells (OPCs) to mature oligodendrocytes modifies the cellular response to TNFa and IL-1b. OPCs exhibit a protective response to these cytokines that is manifest by decreased ceramide, increased sphingosine 1-phosphate, and accompanied by increased cell motility and reduced active caspase 3. Mature oligodendrocytes respond to TNFa and IL-1b with an apoptotic phenotype, evidenced by increased ceramide, decreased sphingosine, increased active caspase 3, and fragmented nuclei. Pharmacological inhibition or a targeted genetic deletion of nSMase2 in vivo partially restored the lipid composition of regenerated myelin sheaths, increased myelin thickness, and enhanced myelin compaction. These results indicate that inhibition of nSMase2 selectively improves the quality of new myelin by protecting maturing/myelinating oligodendrocytes. Pharmacological inhibition of nSMase2 following a demyelinating event could stabilize the structure of these newly formed myelin sheaths and protect from secondary demyelination.

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Event Information

April 16, 2019
11:00 am - 12:00 pm
ASRC 1st Floor Seminar Room
85 St. Nicholas Terrace
New York, NY 10031 United States
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