Single Site Fluorination of the GM4 Ganglioside Epitope Upregulates Oligodendrocyte Differentiation

ACS Chem Neurosci. 2018 May 16;9(5):1159-1165. doi: 10.1021/acschemneuro.8b00002. Epub 2018 Feb 7.

Abstract

Relapsing multiple sclerosis is synonymous with demyelination, and thus, suppressing and or reversing this process is of paramount clinical significance. While insulating myelin sheath has a large lipid composition (ca. 70-80%), it also has a characteristically large composition of the sialosylgalactosylceramide gangliosde GM4 present. In this study, the effect of the carbohydrate epitope on oligodendrocyte differentiation is determined. While the native epitope had no impact on oligodendroglial cell viability, a single site OH → F substitution is the structural basis of a significant increase in ATP production that is optimal at 50 μg/mL. From a translational perspective, this subtle change increases the amount of MBP+ oligodendrocytes compared to the control studies and may open up novel therapeutic remyelination strategies.

Keywords: Carbohydrates; fluorine; gangliosides; multiple sclerosis; myelin; oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Demyelinating Diseases / pathology
  • Epitopes
  • Gangliosides / metabolism*
  • Mice, Inbred C57BL
  • Multiple Sclerosis / metabolism
  • Myelin Sheath / pathology
  • Neurogenesis / physiology
  • Oligodendroglia / cytology*
  • Stem Cells / cytology*

Substances

  • Epitopes
  • Gangliosides