NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice.
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.
Mena
M A
MA
Departmento de Neurobiología-Investigación, CIBERned, Hospital Ramón y Cajal, Madrid, Spain. maria.a.mena@hrc.es
Casarejos
M J
MJ
Solano
R
R
Rodríguez-Navarro
J A
JA
Gómez
A
A
Rodal
I
I
Medina
M
M
de Yebenes
J G
JG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D000975:Antioxidants; D000978:Antiparkinson Agents; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein