Lookup NU author(s): Professor Tiago Outeiro
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The oxidation-sensitive chaperone protein DJ-1 has been implicated in several human disorders including cancer and neurodegenerative diseases. During neurodegeneration associated with protein misfolding, such as that observed in Alzheimer's disease and Huntington's disease (HD), both oxidative stress and protein chaperones have been shown to modulate disease pathways. Therefore, we set out to investigate whether DJ-1 plays a role in HD. We found that DJ-1 expression and its oxidation state are abnormally increased in the humanHDbrain, as well as in mouse and cell models of HD. Furthermore, overexpression of DJ-1 conferred protection in vivo against neurodegeneration in yeast and Drosophila. Importantly, the DJ-1 protein directly interacted with an expanded fragment of huntingtin Exon 1 (httEx1) in test tube experiments and in cell models and accelerated polyglutamine aggregation and toxicity in an oxidation-sensitive manner. Our findings clearly establish DJ-1 as a potential therapeutic target for HD and provide the basis for further studies into the role of DJ-1 in protein misfolding diseases. © The Author 2013. Published by Oxford University Press. All rights reserved.
Author(s): Sajjad MU, Green EW, Miller-Fleming L, Hands S, Herrera F, Campesan S, Khoshnan A, Outeiro TF, Giorgini F, Wyttenbach A
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Print publication date: 01/02/2014
Online publication date: 26/09/2013
Acceptance date: 19/09/2013
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
PubMed id: 24070869
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