Targeting of XJB-5-131 to Mitochondria Suppresses Oxidative DNA Damage and Motor Decline in a Mouse Model of Huntington's Disease

Zhiyin Xun, Sulay Rivera-Sánchez, Sylvette Ayala-Peña, James Lim, Helen Budworth, Erin M. Skoda, Paul D. Robbins, Laura J. Niedernhofer, Peter Wipf, Cynthia T. McMurray

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Oxidative damage and mitochondrial dysfunction are implicated in aging and age-related neurodegenerative diseases, including Huntington@s disease (HD). Many naturally occurring antioxidants have been tested for their ability to correct for deleterious effects of reactive oxygen species, but often they lack specificity, are tissue variable, and have marginal efficacy in human clinical trials. To increase specificity and efficacy, we have designed a synthetic antioxidant, XJB-5-131, to target mitochondria. We demonstrate in a mouse model of HD that XJB-5-131 has remarkably beneficial effects. XJB-5-131 reduces oxidative damage to mitochondrial DNA, maintains mitochondrial DNA copy number, suppresses motor decline and weight loss, enhances neuronal survival, and improves mitochondrial function. The findings poise XJB-5-131 as a promising therapeutic compound.

Original languageEnglish (US)
Pages (from-to)1137-1142
Number of pages6
JournalCell reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012
Externally publishedYes

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