Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice

Int Immunopharmacol. 2016 Oct;39:287-294. doi: 10.1016/j.intimp.2016.07.036. Epub 2016 Aug 5.

Abstract

Nicotinamide adenine dinucleotide (NAD(+)) plays vital roles in mitochondrial functions, cellular energy metabolism and calcium homeostasis. In this study, we investigated the effect of NAD(+) administration for the treatment of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. EAE, a classical animal model of multiple sclerosis (MS), was induced by subcutaneous injection of myelin oligodendrocyteglycoprotein (MOG). The mice were treated with 250mg/kg (body weight) NAD(+) in PBS administered intraperitoneally once daily. We observed that NAD(+) treatment could lessen the severity of EAE. Additionally, NAD(+) treatment attenuated pathological injuries of EAE mice. We also found that the AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1(SIRT1) pathway was activated in the NAD(+)-treated mice and NAD(+) treatment suppressed pro-inflammatory T cell responses. Our findings demonstrated that NAD(+) could be an effective and promising agent to treat multiple sclerosis and its effects on other autoimmune diseases should be explored.

Keywords: AMPK/SIRT1; Experimental autoimmune encephalomyelitis; Immunomodulatory effect; Multiple sclerosis; NAD(+).

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Female
  • Humans
  • Inflammation / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / drug therapy*
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • NAD / therapeutic use*
  • Signal Transduction / drug effects
  • Sirtuin 1 / metabolism*
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th17 Cells / drug effects*

Substances

  • Myelin-Oligodendrocyte Glycoprotein
  • NAD
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1