Protective effect of D609 against amyloid-beta_1-42-induced oxidative modification of neuronal proteins: Redox proteomics study

Oxidative stress has been implicated in the pathophysiology of a number of diseases, including neurodegenerative disorders such as Alzheimer's disease (AD), a neurodegenerative disorder associated with cognitive decline and enhanced oxidative stress. Amyloid-beta peptide_1-42 (Aβ_1-42), one of the main component of senile plaques, can induce in vitro and in vivo oxidative damage to neuronal cells through its ability to produce free radicals. The aim of this study was to investigate the protective effect of the xanthate D609 on Aβ_1-42-induced protein oxidation by using a redox proteomics approach. D609 was recently found to be a free radical scavenger and antioxidant. In the present study, rat primary neuronal cells were pretreated with 50 μM of D609, followed by incubation with 10 μM Aβ_1-42 for 24 hr. In the cells treated with Aβ_1-42 alone, four proteins that were significantly oxidized were identified: glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, malate dehydrogenase, and 14-3-3 zeta. Pretreatment of neuronal cultures with D609 prior to Aβ_1-42 protected all the identified oxidized proteins in the present study against Aβ_1-42-mediated protein oxidation. Therefore, D609 may ameliorate the Aβ_1-42-induced oxidative modification. We discuss the implications of these Aβ_1-42-mediated oxidatively modified proteins for AD pathology and for potential therapeutic intervention in this dementing disorder.