Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease.
Enviado por Sylvette Ayala-Peña el
Título | Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Autores | Xun, Z, Rivera-Sánchez, S, Ayala-Peña, S, Lim, J, Budworth, H, Skoda, EM, Robbins, PD, Niedernhofer, LJ, Wipf, P, McMurray, CT |
Journal | Cell Rep |
Volume | 2 |
Issue | 5 |
Pagination | 1137-42 |
Date Published | 2012 Nov 29 |
ISSN | 2211-1247 |
Palabras clave | Animals, Antioxidants, Cell Survival, Cells, Cultured, Cyclic N-Oxides, Disease Models, Animal, DNA Damage, DNA, Mitochondrial, Gene Dosage, Huntington Disease, Mice, Mice, Inbred C57BL, Mitochondria, Motor Activity, Neurons, Oxidative Stress, Weight Loss |
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. |
DOI | 10.1016/j.celrep.2012.10.001 |
Alternate Journal | Cell Rep |
PubMed ID | 23122961 |
PubMed Central ID | PMC3513647 |
Grant List | AG024827 / AG / NIA NIH HHS / United States AI068021 / AI / NIAID NIH HHS / United States AR051456 / AR / NIAMS NIH HHS / United States CA092584 / CA / NCI NIH HHS / United States ES016114 / ES / NIEHS NIH HHS / United States GM066359 / GM / NIGMS NIH HHS / United States GM067082 / GM / NIGMS NIH HHS / United States NS060115 / NS / NINDS NIH HHS / United States NS062384 / NS / NINDS NIH HHS / United States NS40738 / NS / NINDS NIH HHS / United States P01 CA092584 / CA / NCI NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States R01 ES020766 / ES / NIEHS NIH HHS / United States R01 GM066359 / GM / NIGMS NIH HHS / United States R01 NS060115 / NS / NINDS NIH HHS / United States R01 NS062384 / NS / NINDS NIH HHS / United States |