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BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access October 22, 2010

Potential application of grape derived polyphenols in Huntington’s disease

  • Jun Wang EMAIL logo , Cathie Pfleger , Lauren Friedman , Roselle Vittorino , Wei Zhao , Xianjuan Qian , Lindsay Conley , Lap Ho and Giulio Pasinetti

Abstract

Huntington’s disease (HD) is a progressive neurodegenerative disorder associated with selective neuronal cell death. Abnormal aggregation of huntingtin protein with polyQ expansion has been shown to be causally linked to HD. Grape seed polyphenolic extract (GSPE) is a natural compound that has previously been shown to interfere with aggregations of proteins involved in neurological disorders, such as amyloid beta peptides (Aβ) and Tau protein. In this study we found that GSPE treatment significantly inhibits polyQ aggregation in phaeochromocytoma (PC)-12 cell line containing an ecdysone-inducible protein comprising the first 17 amino acid of huntingtin plus 103 glutamines fused with enhanced GFP. In vivo feasibility studies using the Q93httexon1 drosophila model of HD, we extended our in vitro evidence and found that flies fed with GSPE had a significantly improved lifespan compared to the control flies. Using the R6/2 rodent model of HD, we found that oral administration of 100 mg/kg/day GSPE (equivalent to 500mg per day in human) significantly attenuated the motor skill decay as well as extended the lifespan in the R6/2 mice relative to vehicle-control mice. Collectively, our studies strongly suggest that GSPE might be able to modulate the onset and/or progression of HD.

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Published Online: 2010-10-22
Published in Print: 2010-6-1

© 2010 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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