title: Reagents that block neuronal death from Huntington's disease also curb oxidative stress.
abstract: Patients with Huntington's disease suffer severe neuronal loss and signs of oxidative damage in the brain. Previously we found that primary neurons from embryonic cortex of mice bearing the Huntington's disease mutation (140 glutamines inserted into exon 1 of huntingtin) showed higher levels of reactive oxygen species before cell death. Here, we treated mutant neurons with known neuroprotective agents and determined the effects on neuronal survival and levels of reactive oxygen species. Primary neurons were exposed to the neurotrophin, brain derived neurotrophic factor, the antioxidant N-acetyl-cysteine or a specific inhibitor of glycogen synthase kinase 3-β, SB216763. Each reagent increased the survival of the mutant neurons compared with untreated mutant neurons and also reduced the levels of reactive oxygen species to levels of wild-type neurons. These results suggest that reducing the levels of reactive oxygen species may be necessary to protect neurons with the Huntington's disease mutation from cell death.
authors: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Antonio
authors: A
authors: Valencia
authors: Ellen
authors: E
authors: Sapp
authors: Patrick B
authors: PB
authors: Reeves
authors: Jonathan
authors: J
authors: Alexander
authors: Nicholas
authors: N
authors: Masso
authors: Xueyi
authors: X
authors: Li
authors: Kimberly B
authors: KB
authors: Kegel
authors: Marian
authors: M
authors: DiFiglia
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3