Journal Article

Meclizine is neuroprotective in models of Huntington's disease

Vishal M. Gohil, Nicolas Offner, James A. Walker, Sunil A. Sheth, Elisa Fossale, James F. Gusella, Marcy E. MacDonald, Christian Neri and Vamsi K. Mootha

in Human Molecular Genetics

Volume 20, issue 2, pages 294-300
Published in print January 2011 | ISSN: 0964-6906
Published online October 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq464
Meclizine is neuroprotective in models of Huntington's disease

Show Summary Details

Preview

Defects in cellular energy metabolism represent an early feature in a variety of human neurodegenerative diseases. Recent studies have shown that targeting energy metabolism can protect against neuronal cell death in such diseases. Here, we show that meclizine, a clinically used drug that we have recently shown to silence oxidative metabolism, suppresses apoptotic cell death in a murine cellular model of polyglutamine (polyQ) toxicity. We further show that this protective effect extends to neuronal dystrophy and cell death in Caenorhabditis elegans and Drosophila melanogaster models of polyQ toxicity. Meclizine's mechanism of action is not attributable to its anti-histaminergic or anti-muscarinic activity, but rather, strongly correlates with its ability to suppress mitochondrial respiration. Since meclizine is an approved drug that crosses the blood–brain barrier, it may hold therapeutic potential in the treatment of polyQ toxicity disorders, such as Huntington's disease.

Journal Article.  3982 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.