NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice

FEBS Lett. 2009 Jan 5;583(1):168-74. doi: 10.1016/j.febslet.2008.11.051. Epub 2008 Dec 10.

Abstract

Parkin mutations produce Parkinson's disease (PD) in humans and nigrostriatal dopamine lesions related to increased free radicals in mice. We examined the effects of NP7, a synthetic, marine derived, free radical scavenger which enters the brain, on H(2)O(2) toxicity in cultured neurons and glia from wild-type (WT) and parkin null mice (PK-KO). NP7, 5-10 microM, prevented the H(2)O(2) induced apoptosis and necrosis of midbrain neuronal and glial cultures from WT and PK-KO mice. NP7 suppressed microglial activation and the H(2)O(2) induced drop-out of dopamine neurons(.) Furthermore, NP7 prevented the increased phosphorylation of ERK and AKT induced by H(2)O(2). NP7 may be a promising neuroprotector against oxidative stress in PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antiparkinson Agents / pharmacology*
  • Cells, Cultured
  • Cytoprotection*
  • Free Radical Scavengers / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • Mesencephalon / cytology
  • Mesencephalon / drug effects*
  • Mice
  • Mice, Knockout
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neurons / cytology
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Antioxidants
  • Antiparkinson Agents
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Hydrogen Peroxide
  • Ubiquitin-Protein Ligases
  • parkin protein