Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

Human Molecular Genetics
Aris PolyzosCynthia T McMurray

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.

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Citations

Aug 2, 2016·Cell Chemical Biology·Simon WisnovskyShana O Kelley
Sep 17, 2016·Mechanisms of Ageing and Development·Aris A Polyzos, Cynthia T McMurray
Sep 19, 2016·Biochemical and Biophysical Research Communications·Géraldine LiotEmmanuel Brouillet
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Jan 12, 2019·Neurotoxicity Research·Musthafa Mohamed EssaMohammed Akbar
Dec 17, 2020·Journal of Huntington's Disease·Marcus P J van DiemenGeert Jan Groeneveld
Sep 6, 2018·ACS Chemical Biology·Tanja KrainzRobert S B Clark

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