Antioxidant activity of X-34 in synaptosomal and neuronal systems

Inhibiting aggregation and deposition of amyloid beta-peptide (Abeta) in brain is a therapeutic strategy for Alzheimer's disease (AD). A Congo-red-like molecule, X-34, is reported to bind to Abeta deposits. Oxidative stress associated with Abeta is hypothesized to be critical for the neurotoxic properties of this peptide. The present study was undertaken to test the hypothesis that X-34, with its salicylate groups, would act as an antioxidant. When challenged by hydroxyl or peroxyl free radicals or Abeta(1-42), oxidative stress and neurotoxicity occurred in neural systems as assessed by several indices. However, pretreatment of synaptosomes and primary neuronal cell culture with X-34 greatly ameliorated lipid peroxidation induced by these free radicals and Abeta(1-42). Protein oxidation was not prevented by X-34. These results are discussed in terms of potential therapeutic use of X-34 and related compounds in AD.