A novel treatment target for Parkinson's disease

J Neurol Sci. 2014 Dec 15;347(1-2):34-8. doi: 10.1016/j.jns.2014.10.024. Epub 2014 Oct 23.

Abstract

We hypothesize that GPR109A message and expression are up-regulated in individuals with Parkinson's disease (PD). GPR109A is a high-affinity niacin receptor. Niacin is a precursor for NAD-NADH which is needed for dopamine production. Thus, niacin supplementation may serve three purposes: reduce inflammation through GPR109A-related mechanisms, increase dopamine synthesis in the striatum through NADPH supply and increase NAD/NADH ratio to boost mitochondrial functions. GPR109A and its agonists are known to exert anti-inflammatory actions in the skin, gut and retina. However these roles are neither anticipated nor established in the CNS. For the first time here we propose the roles of GPR109A and its agonists including niacin in CNS pathology. Moreover we predict that the neuroprotective roles of either niacin or butyrates in CNS occur via GPR109A.

Keywords: GPR109A; HCAR2; HM74a; Inflammation; Niacin; Niacinamide.

Publication types

  • Review

MeSH terms

  • Aged
  • Dopamine / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • NAD / metabolism
  • Neuroprotective Agents / pharmacology
  • Niacin / metabolism
  • Niacin / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Up-Regulation*

Substances

  • HCAR2 protein, human
  • Neuroprotective Agents
  • Nicotinic Agonists
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • NAD
  • Niacin
  • Dopamine