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

Autor: 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
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Cell Reports, Vol 2, Iss 5, Pp 1137-1142 (2012)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2012.10.001
Popis: 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.
Databáze: Directory of Open Access Journals