The Johns Hopkins University School of Medicine
Inhibition of neutral sphingomyelinase 2 promotes remyelination
펼치기 Authors and Affiliations
Abstract

Myelination requires a highly organized synthesis of multiple lipid species that regulate myelin curvature and compaction. For reasons that are not understood, central nervous system remyelinated axons often have thin myelin sheaths with a disorganized structure susceptible to secondary demyelination. We found that expression of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) during the differentiation of oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes changes their response to inflammatory cytokines. OPCs do not express nSMase2 and exhibit a protective/regenerative response to tumor necrosis factor–α and interleukin-1β. Oligodendrocytes express nSMase2 and exhibit a stress response to cytokine challenge that includes an overproduction of ceramide, a sphingolipid that forms negative curvatures in membranes. Pharmacological inhibition or genetic deletion of nSMase2 in myelinating oligodendrocytes normalized the ceramide content of remyelinated fibers and increased thickness and compaction. These results suggest that inhibition of nSMase2 could improve the quality of myelin and stabilize structure.

주소복사
논문정보   
- 형식: Research article
- 게재일: 2020년 10월 (BRIC 등록일 2020-10-06)
- 연구진: 국외연구진
- 분야: Neuroscience
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