Targeting of XJB-5-131 to Mitochondria Suppresses Oxidative DNA Damage and Motor Decline in a Mouse Model of Huntington’s Disease
Year: 2012
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Institute on Minority Health and Health Disparities
Awards: G1054907967, New Concepts, Methodologies and Scaffolds for Diversity-Oriented Organic Synthes, Signature-Directed, Sequential Delivery of Radiation Mitigators, G1341132670, G1566366320, Mismatch Repair and DNA expansion, G242268698, G2680263196, G3494281971, G4306979152, Trafficking Defects in Huntingtons Disease, LMP and Bone Healing, G5785919769, Age of Onset and Huntingtons Disease, The contribution of DNA interstrand crosslinks to aging, Integrating Cancer and Aging, Center for Collaborative Research in Health Disparities, G717815140, G736261140, Metabolic markers for mitochondrial function, G8241934473, Center for Collaborative Research in Health Disparities, G8438412112, Pittsburgh Older Americans Independence Center, Structural Cell Biology of DNA Repair Machines
OpenAlex ID: W2129431237