Activation of group II metabotropic glutamate receptors underlies microglial reactivity and neurotoxicity following stimulation with chromogranin A, a peptide up-regulated in Alzheimer's disease.

摘要: Regulation of microglial reactivity and neurotoxicity is critical for neuroprotection in neurodegenerative diseases. Here we report that microglia possess functional group II metabotropic glutamate receptors, expressing mRNA receptor protein mGlu2 mGlu3, negatively coupled to adenylate cyclase. Two different agonists these receptors were able induce a neurotoxic phenotype which was attenuated by specific antagonist. Chromogranin A, secretory peptide expressed amyloid plaques Alzheimer's disease, activates reactive phenotype. A-induced activation subsequent may also involve an underlying stimulation since their inhibition reduced chromogranin neurotoxicity. These results show selective has positive impact on neuronal survival, prove therapeutic target disease.