Methylcobalamin prevents mutant superoxide dismutase-1-induced motor neuron death in vitro

Neuroreport. 2017 Jan 18;28(2):101-107. doi: 10.1097/WNR.0000000000000716.

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disorder that causes motor dysfunction. Treatments and drugs that slow progression of ALS have garnered great interest. In the present study, we show that the vitamin B12 analog methylcobalamin (MBL) effectively and dose dependently prevented embryonic stem cell-derived motor neuron death induced by cocultivation with astrocytes expressing mutant human superoxide dismutase-1 (G93A). Moreover, cotreatment of MBL with a conventional ALS drug, riluzole, further enhanced survival of motor neurons in this in-vitro ALS model. Our results show the potential use of MBL as a treatment for ALS and suggest a possible combination therapy strategy with other types of approved ALS drugs.

MeSH terms

  • Animals
  • Cell Death / drug effects*
  • Cell Death / genetics
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Embryo, Mammalian
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Transgenic
  • Motor Neurons / drug effects*
  • Motor Neurons / physiology*
  • Neuroprotective Agents / pharmacology
  • Riluzole / pharmacology
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Vitamin B 12 / analogs & derivatives*
  • Vitamin B 12 / pharmacology
  • Vitamin B Complex / pharmacology*

Substances

  • Neuroprotective Agents
  • Vitamin B Complex
  • Riluzole
  • mecobalamin
  • SOD1 G93A protein
  • Superoxide Dismutase
  • Vitamin B 12