New Lipoxygenase Inhibitors of Reactive Oxygen Species Production in Cellular Models of Amyloid (A 2 ) Toxicities

Abstract

Neuroinflammation and oxidative stress are contributing factors to neurodegeneration in physiological aging as well as in age-related neurological disorders. Neuroinflammation can be both a cause and a result of chronic oxidative stress. The role of the oxidative stress and free radicals in the development of Alzheimer's disease (AD) is currently the focus of many studies. Hydrogen peroxide (H₂O₂) in AD is thought to be associated with amyloid-β (Aβ) damage in cells. Aryl acetic acid derivatives were previously reported to be potent anti-inflammatory and antioxidant agents. In the present study, aryl acetic acid derivatives were tested as H₂O₂ scavengers using the DCF assay on two types of neuronal cells: a) the wild type N2a neuroblastoma cells; and b) the AβPP/PS1 transgenic cell line expressing Aβ. The scavenging activity of these agents and their protective role against cell death was demonstrated in both cell types. Our results suggest that these compounds could be used as a template in the design of novel therapeutic agents for AD.