Pioglitazone activates paraoxonase-2 in the brain: A novel neuroprotective mechanism

Exp Neurol. 2020 May:327:113234. doi: 10.1016/j.expneurol.2020.113234. Epub 2020 Feb 7.

Abstract

Paraoxonase-2 regulates reactive oxygen species production in mitochondria. Stimulating its expression has therapeutic potential for diseases where oxidative stress plays a significant role in the pathology. Evidence suggests that the anti-diabetic drug pioglitazone may provide neuroprotection in Parkinson's disease, Alzheimer's disease, brain trauma and ischemia, but the biochemical pathway(s) responsible has not been fully elucidated. Here we report that pioglitazone (10 mg/kg/day) for 5 days significantly increased paraoxonase-2 expression in mouse striatum. Thus, this result highlights paraoxonase-2 as a target for neuroprotective strategies and identifies pioglitazone as a tool to study the role of paraoxonase-2 in brain.

Keywords: Neuroprotection; Oxidative stress; Paraoxonase-2; Parkinson's disease; Peroxisome proliferator-activated receptor gamma; Pioglitazone; Striatum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aryldialkylphosphatase / metabolism*
  • Brain / drug effects*
  • Brain / metabolism
  • Male
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Pioglitazone / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Up-Regulation / drug effects

Substances

  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Aryldialkylphosphatase
  • Pioglitazone