title: N-acteyl cysteine alleviates oxidative damage to central nervous system of ApoE-deficient mice following folate and vitamin E-deficiency.
abstract: Oxidative stress is an early neurodegenerative insult in Alzheimer's disease (AD). Antioxidant mechanisms, including elements of the glutathione (GSH) pathway, undergo at least a transient compensatory increase that is apparently insufficient due to continued oxidative damage during disease progression. Mice deficient in apolipoprotein E, which provide a model for some aspects of AD, undergo increased oxidative damage to brain tissue and cognitive decline when maintained on a folate-free diet, despite a compensatory increase in glutathione synthase transcription and activity as well as increased levels of GSH. Dietary supplementation with N-acetyl cysteine (1 g/kg diet), a cell-permeant antioxidant and GSH precursor, alleviated oxidative damage and cognitive decline, and restored glutathione synthase and GSH levels in ApoE-deficient mice deprived of folate to those of normal mice maintained in the presence of folate. These data support the administration of antioxidant precursors to buffer oxidative damage in neurodegenerative disorders.
authors.affiliation: Center for Cellular Neurobiology and Neurodegeneration Research Departments of University of Massachusetts Lowell Lowell, MA 01854, USA.
authors.forename: Flaubert
authors.initials: F
authors.lastname: Tchantchou
authors.forename: Michael
authors.initials: M
authors.lastname: Graves
authors.forename: Eugene
authors.initials: E
authors.lastname: Rogers
authors.forename: Daniela
authors.initials: D
authors.lastname: Ortiz
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D014811:Vitamin E Deficiency / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D005492:Folic Acid; D000111:Acetylcysteine