Metabotropic glutamate receptors: targets for neuroprotective therapies in Parkinson disease

• Type of Material: Article
• Authors: Gunasingh J Masilamoni, Emory University; Yoland Smith, Emory University
• Language: English
• Date: 2018-02-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.coph.2018.03.004
• Title of Journal or Parent Work: Current Opinion in Pharmacology
• ISSN: 1471-4892
• Volume: 38
• Start Page: 72
• End Page: 80
• Keywords: RAT; Pharmacology & Pharmacy; BASAL-GANGLIA; NMDA RECEPTORS; ACTIVATION; Life Sciences & Biomedicine; 5 ANTAGONIST; IMMUNOHISTOCHEMICAL LOCALIZATION; INDUCED DYSKINESIA; Science & Technology; EXCITATORY TRANSMISSION; NEURONS; MICROGLIAL NEUROTOXICITY
• Research Categories: Health Sciences, Toxicology; Health Sciences, Immunology; Health Sciences, Pharmacology

Abstract

Metabotropic glutamate receptors (mGluRs) are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release and long term synaptic plasticity. Therefore, targeting specific mGluR subtypes by means of selective drugs could be a possible strategy for restoring normal synaptic function and neuronal activity of the BG in Parkinson disease (PD). Preclinical studies have revealed that specific mGluR subtypes mediate significant neuroprotective effects that reduce toxin-induced midbrain dopaminergic neuronal death in animal models of PD. Although the underlying mechanisms of these effects must be further studied, there is evidence that intracellular calcium regulation, anti-inflammatory effects, and glutamatergic network modulation contribute to some of these neuroprotective properties. It is noteworthy that these protective effects extend beyond midbrain dopaminergic neurons to include other monoaminergic cell groups for some mGluRs. In this review, we discuss evidence for mGluR-mediated neuroprotection in PD and highlight the challenges to translate these findings into human trials.