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

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• 作者：William DeCoteau ; PhD^a ; ¹ ; Karin L. Heckman ; PhD^b ; ¹ ; Ana Y. Estevez ; PhD^a ; ^b ; Kenneth J. Reed ; PhD^c ; Wendi Costanzo ; BS^c ; David Sandford ; BA^c ; Paige Studlack ; BA^a ; Jennifer Clauss ; BA^b ; Elizabeth Nichols ; BA^b ; Jennifer Lipps ; BA^b ; Matthew Parker ; BA^b ; Bonnie Hays-Erlichman ; BA^b ; J.C. Leiter ; MD^d ; ^{james.c.leiter@dartmouth.edu" class="auth_mail" title="E-mail the corresponding author} ; Joseph S. Erlichman ; PhD^b
• 关键词：Oxidative stress ; Cerium oxide nanoparticles ; Amyotrophic lateral sclerosis
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：12
• 期：8
• 页码：2311-2320
• 全文大小：729 K

文摘

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 SOD1^G93A mouse model of ALS, we tested whether administration of CeNPs would improve survival and reduce disease severity in SOD1^G93A transgenic mice. Twice a week intravenous treatment of SOD1^G93A 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 ± 3.7 days (N = 20), and only 22.0 ± 2.5 days 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 SOD1^G93A mice.