Chemoenzymatically synthesized GM3 analogues as potential therapeutic agents to recover nervous functionality after injury by inducing neurite outgrowth

Eur J Med Chem. 2018 Feb 25:146:613-620. doi: 10.1016/j.ejmech.2018.01.079. Epub 2018 Jan 31.

Abstract

Ganglioside GM3 is implicated in a variety of physiological and pathological processes. Due to GM3 exposes on the outer surface of cell membranes, it is strongly associated with cell adhesion, motility and differentiation. Neurite outgrowth is a key process in the development of functional neuronal circuits and regeneration of the nervous system after injury. In the present study, we used enzymatic hydrolysis and chemical synthesis to obtain novel galactose containing GM3 analogues. By enzymatic hydrolysis to prepare GM3 building block, we can avoid multiple chemical procedures. Next, we employed the PC12 cells as a model to evaluate the effects of GM3 analogues on neurite outgrowth with or without NGF induction. The biological tests showed that GM3 analogues could induce neurite outgrowth, which provides the valuable sights for potential nervous system treatment after injury.

Keywords: Chemoenzymatic synthesis; Ganglioside GM3; Neurite outgrowth; PC12 cells.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • G(M3) Ganglioside / chemical synthesis
  • G(M3) Ganglioside / chemistry
  • G(M3) Ganglioside / pharmacology*
  • Hydrolysis
  • Molecular Structure
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • PC12 Cells
  • Rats
  • Structure-Activity Relationship

Substances

  • G(M3) Ganglioside