Journal article

Mechanisms of Copper Ion Mediated Huntington's Disease Progression

Jonathan H Fox, Jibrin A Kama, Gregory Lieberman, Raman Chopra, Kate Dorsey, Vanita Chopra, Irene Volitakis, Robert A Cherny, Ashley I Bush, Steven Hersch

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2007

Abstract

Huntington's disease (HD) is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgenic mice. Increased brain copper correlated with decreased levels of the copper export protein, amyloid precursor protein. We hypothesized that increased amounts of copper bound to low affinity sites could..

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Grants

Awarded by NIH/NINDS


Awarded by NIH/NCCAM


Awarded by NATIONAL CENTER FOR COMPLEMENTARY &ALTERNATIVE MEDICINE


Awarded by National Center for Complementary & Integrative Health


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

Support was provided by the Huntington's Disease Society of America (HDSA), The HighQ Foundation, NIH/NINDS (NS35255 and NS045242) and NIH/NCCAM (AT00613). The Australian Research Council and the National Health and Research Council of Australia supported RAC, IV and AIB.