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peterz54
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Date Joined Apr 2010
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   Posted 6/27/2010 9:47 PM (GMT -4)    Quote This PostAlert An Admin About This Post.
New paper suggesting that some antioxidants inhibit autophagy.
will try to get entire paper
 
Hum Mol Genet. 2010 Jun 21. [Epub ahead of print]
ANTIOXIDANTS CAN INHIBIT BASAL AUTOPHAGY AND ENHANCE NEURODEGENERATION IN MODELS OF POLYGLUTAMINE DISEASE.

Underwood BR, Imarisio S, Fleming A, Rose C, Krishna G, Heard P, Quick M, Korolchuk VI, Renna M, Sarkar S, García-Arencibia M, O'Kane CJ, Murphy MP, Rubinsztein DC.

Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, U.K.
Abstract

Many neurodegenerative diseases exhibit protein accumulation and increased oxidative stress. Therapeutic strategies include clearing aggregate-prone proteins by enhancing autophagy or decreasing oxidative stress with antioxidants. Many autophagy-inducing stimuli increase reactive oxygen species (ROS), raising concerns that the benefits of autophagy up-regulation may be counterbalanced by ROS toxicity. Here we show that not all autophagy inducers significantly
increase ROS. However, many antioxidants inhibit both basal and induced autophagy. By blocking autophagy, antioxidant drugs can increase the levels of aggregate-prone proteins associated with neurodegenerative disease. In fly and zebrafish models of Huntington's disease, antioxidants exacerbate the disease phenotype and abrogate the rescue seen with autophagy-inducing agents. Thus, the potential benefits in neurodegenerative diseases of some classes of antioxidants may be compromised by their autophagy-blocking properties.

PMID: 20566712

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