Journal article
N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease
DJ Wright, T Renoir, ZM Smith, AE Frazier, PS Francis, DR Thorburn, SL McGee, AJ Hannan, LJ Gray
Translational Psychiatry | Published : 2015
DOI: 10.1038/tp.2014.131
Abstract
Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an ant..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Peter Crouch for his insightful feedback and the Australian Mitochondrial Disease Foundation for partial support of purchasing the Seahorse XF24 Extracellular Flux Analyzer. The Florey Institute of Neuroscience and Mental Health acknowledges the support from the Victorian Government's Operational Infrastructure Support Grant. This work was supported by an Australian Research Council FT3 Future Fellowship (FT100100835) to AJH, National Health and Medical Research Council Career Development Fellowships to SLM (APP1030474) and AEF (APP541920) and a National Health and Medical Research Council Principal Research Fellowship to DRT (APP1022896). DJW holds a University of Melbourne Australian Postgraduate Award. TR is supported by an Australian Research Council Discovery Early Career Research Award (DE140100588).