Cerium oxide nanoparticles with antioxidant properties ameliorate strength and prolong life in mouse model of amyotrophic lateral sclerosis

Abstract

Cerium oxide nanoparticles (CeNPs) neutralize reactive oxygen and nitrogen species. Since oxidative stress plays a role in amyotrophic lateral sclerosis (ALS) in humans and in the SOD1G93A mouse model of ALS, we tested whether administration of CeNPs would improve survival and reduce disease severity in SOD1G93A transgenic mice. Twice a week intravenous treatment of SOD1G93A mice with CeNPs started at the onset of muscle weakness preserved muscle function and increased longevity in males and females. Median survival after the onset of CeNP treatment was 33.0±3.7days (N=20), and only 22.0±2.5days in mice treated with vehicle, control injections (N=27; P=0.022). Since these citrate–EDTA stabilized CeNPs exhibited catalase and oxidase activity in cell-free systems and in in vitro models of ischemic oxidative stress, we hypothesize that antioxidant activity is the protective mechanism prolonging survival in the SOD1G93A mice.