Antiapoptotic signaling by a remyelination-promoting human antimyelin antibody

Charles L. Howe, Allan J. Bieber, Arthur E. Warrington, Larry R. Pease, Moses Rodriguez

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Stabilizing the survival of oligodendrocytes and oligodendrocyte precursors within and near lesions in patients suffering from multiple sclerosis (MS) and other demyelinating diseases is an important therapeutic goal. Previous studies have identified a human-derived monoclonal IgM antibody designated rHIgM22 that induces remyelination in a mouse model of MS. We provide evidence that this antibody, directed against myelin, induces antiapoptotic signaling in premyelinating oligodendrocytes and reduces caspase-3 activation and caspase gene expression in mice undergoing antibody-induced remyelination. This effect was dependent on calcium entry via CNQX-sensitive channels and on lipid raft integrity, and was correlated with suppression of JNK signaling. We conclude that rHIgM22 may induce remyelination via rescue of oligodendrocytes, and suggest that such autoantibody-mediated signaling may have important therapeutic implications for a variety of neurological diseases, including stroke and Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)120-131
Number of pages12
JournalNeurobiology of Disease
Volume15
Issue number1
DOIs
StatePublished - Feb 2004

Keywords

  • Apoptosis
  • Autoantibody
  • Demyelinating disease
  • Glia
  • Multiple sclerosis
  • Myelin

ASJC Scopus subject areas

  • Neurology

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