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High Content Screening in Neurodegenerative Diseases
Published on: January 6, 2012
DJ-1 modulates aggregation and pathogenesis in models of Huntington's disease
Muhammad U Sajjad1, Edward W Green, Leonor Miller-Fleming
1Neuroscience Group, Centre for Biological Sciences, University of Southampton, Basset Crescent East, Southampton, UK.
Human Molecular Genetics
|September 28, 2013
Summary
The chaperone protein DJ-1 is elevated in Huntington
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- DJ-1 is an oxidation-sensitive chaperone protein linked to neurodegenerative diseases.
- Oxidative stress and chaperones influence protein misfolding diseases like Alzheimer's and Huntington's disease (HD).
Purpose of the Study:
- To investigate the role of DJ-1 in the pathogenesis of Huntington's disease.
Main Methods:
- Examined DJ-1 expression and oxidation state in human HD brain and HD models.
- Assessed DJ-1's protective effects in vivo using yeast and Drosophila models.
- Investigated DJ-1's interaction with huntingtin exon 1 (httEx1) and its effect on polyglutamine aggregation.
Main Results:
- DJ-1 expression and oxidation were abnormally increased in HD models.
- Overexpression of DJ-1 provided protection against neurodegeneration.
- DJ-1 directly interacted with httEx1, accelerating aggregation and toxicity in an oxidation-sensitive manner.
Conclusions:
- DJ-1 plays a significant role in Huntington's disease pathogenesis.
- DJ-1 is a potential therapeutic target for Huntington's disease and other protein misfolding disorders.
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