Format

Send to

Choose Destination
Hum Mol Genet. 2011 Jan 15;20(2):294-300. doi: 10.1093/hmg/ddq464. Epub 2010 Oct 25.

Meclizine is neuroprotective in models of Huntington's disease.

Author information

1
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA. vgohil@chgr.mgh.harvard.edu

Abstract

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.

PMID:
20977989
PMCID:
PMC3005902
DOI:
10.1093/hmg/ddq464
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center