Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes
Abstract
Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a graying phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.
- Authors:
-
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Univ. of California, Berkeley, CA (United States)
- Univ. of Pittsburgh, PA (United States)
- Consejo Superior de Investigaciones Cientificas (CSIC), Madrid (Spain)
- Univ. of Puerto Rico, San Juan, PR (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH); USDOE
- OSTI Identifier:
- 1379313
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Human Molecular Genetics
- Additional Journal Information:
- Journal Volume: 25; Journal Issue: 9; Journal ID: ISSN 0964-6906
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Polyzos, Aris, Holt, Amy, Brown, Christopher, Cosme, Celica, Wipf, Peter, Gomez-Marin, Alex, Castro, Maríadel R., Ayala-Peña, Sylvette, and McMurray, Cynthia T. Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes. United States: N. p., 2016.
Web. doi:10.1093/hmg/ddw051.
Polyzos, Aris, Holt, Amy, Brown, Christopher, Cosme, Celica, Wipf, Peter, Gomez-Marin, Alex, Castro, Maríadel R., Ayala-Peña, Sylvette, & McMurray, Cynthia T. Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes. United States. https://doi.org/10.1093/hmg/ddw051
Polyzos, Aris, Holt, Amy, Brown, Christopher, Cosme, Celica, Wipf, Peter, Gomez-Marin, Alex, Castro, Maríadel R., Ayala-Peña, Sylvette, and McMurray, Cynthia T. Sun .
"Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes". United States. https://doi.org/10.1093/hmg/ddw051. https://www.osti.gov/servlets/purl/1379313.
@article{osti_1379313,
title = {Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes},
author = {Polyzos, Aris and Holt, Amy and Brown, Christopher and Cosme, Celica and Wipf, Peter and Gomez-Marin, Alex and Castro, Maríadel R. and Ayala-Peña, Sylvette and McMurray, Cynthia T.},
abstractNote = {Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a graying phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.},
doi = {10.1093/hmg/ddw051},
journal = {Human Molecular Genetics},
number = 9,
volume = 25,
place = {United States},
year = {Sun Feb 21 00:00:00 EST 2016},
month = {Sun Feb 21 00:00:00 EST 2016}
}
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