Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease.

ABSTRACT:

Background and purpose

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. We have previously demonstrated that the cell signalling of the metabotropic glutamate receptor 5 (mGluR5) is altered in a mouse model of HD. Although mGluR5-dependent protective pathways are more activated in HD neurons, intracellular Ca²⁺ release is also more pronounced, which could contribute to excitotoxicity. In the present study, we aim to investigate whether mGluR5 positive allosteric modulators (PAMs) could activate protective pathways without triggering high levels of Ca²⁺ release and be neuroprotective in HD.

Experimental approach

We performed a neuronal cell death assay to determine which drugs are neur

SUBMITTER: Doria JG 

PROVIDER: S-EPMC3687670 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature