Oxidative stress kills human primary oligodendrocytes via neutral sphingomyelinase: implications for multiple sclerosis

J Neuroimmune Pharmacol. 2007 Jun;2(2):184-93. doi: 10.1007/s11481-007-9066-2. Epub 2007 Mar 8.


Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system where oxidative stress has been proposed to play an important role in oligodendroglial death. However, molecular mechanisms that couple oxidative stress to the loss of oligodendrocytes are poorly understood. This study underlines the importance of neutral sphingomyelinase-ceramide pathway in mediating oxidative stress-induced apoptosis and cell death of human primary oligodendrocytes. Various oxidative stress-inducing agents, such as, superoxide radical produced by hypoxanthine and xanthine oxidase, hydrogen peroxide, aminotriazole capable of inhibiting catalase and increasing intracellular level of H2O2, or reduced glutathione-depleting diamide induced the activation of neutral sphingomyelinase and the production of ceramide. It is interesting to note that antisense knockdown of neutral but not acidic sphingomyelinase ablated oxidative stress-induced apoptosis and cell death in human primary oligodendrocytes. This study identifies neutral but not acidic sphingomyelinase as a target for possible therapeutic intervention in MS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology*
  • Cell Death / physiology
  • Cells, Cultured
  • Ceramides / physiology
  • Fetus
  • Humans
  • Multiple Sclerosis / enzymology*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology*
  • Oligodendroglia / cytology*
  • Oligodendroglia / enzymology*
  • Oligodendroglia / pathology
  • Oxidative Stress / physiology*
  • Signal Transduction / physiology
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors
  • Sphingomyelin Phosphodiesterase / physiology*


  • Ceramides
  • Sphingomyelin Phosphodiesterase