Agonists of metabotropic glutamate receptors and uses thereof

摘要

Astrocytes protect neurons from excitotoxic injury by maintaining low extra-cellular glutamate concentrations ([Glu]o). Compromised astrocytic glutamate uptake has been implicated in acute and chronic neurological conditions, including Parkinson's disease. This invention provides evidence that [Glu]o is modulated in a feed-back manner through activation of metabotropic glutamate receptors (mGluRs), particularly group II mGluRs. Furthermore, ACPD effects were mimicked by glutamate, suggesting that astrocytic glutamate transport is dynamically regulated with mGluRs acting as sensors for changes in [Glu]. Consequently, agonists of mGluR receptors are potent drugs to modulate extracellular glutamate levels in ways that are neuroprotective.