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Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications.

ABSTRACT: The metabotropic glutamate (mGlu) receptors are a group of Class C seven-transmembrane spanning/G protein-coupled receptors (7TMRs/GPCRs). These receptors are activated by glutamate, one of the standard amino acids and the major excitatory neurotransmitter. By activating G protein-dependent and non-G protein-dependent signaling pathways, mGlus modulate glutamatergic transmission both in the periphery and throughout the central nervous system. Since the discovery of the first mGlu receptor, and especially during the last decade, a great deal of progress has been made in understanding the signaling, structure, pharmacological manipulation and therapeutic indications of the 8 mGlu members.

SUBMITTER: Yin S

PROVIDER: S-EPMC4130774 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications.

Yin Shen S Niswender Colleen M CM

Cellular signalling 20140502 10

The metabotropic glutamate (mGlu) receptors are a group of Class C seven-transmembrane spanning/G protein-coupled receptors (7TMRs/GPCRs). These receptors are activated by glutamate, one of the standard amino acids and the major excitatory neurotransmitter. By activating G protein-dependent and non-G protein-dependent signaling pathways, mGlus modulate glutamatergic transmission both in the periphery and throughout the central nervous system. Since the discovery of the first mGlu receptor, and e ...[more]

PMID: 24793301

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Project description:Metabotropic glutamate receptors (mGlu) are class C G protein-coupled receptors of eight subtypes that are omnipresently expressed in the central nervous system. mGlus have relevance in several psychiatric and neurological disorders, therefore they raise considerable interest as drug targets. Allosteric modulators of mGlus offer advantages over orthosteric ligands owing to their increased potential to achieve subtype selectivity, and this has prompted discovery programs that have produced a large number of reported allosteric mGlu ligands. However, the optimization of allosteric ligands into drug candidates has proved to be challenging owing to induced-fit effects, flat or steep structure-activity relationships and unexpected changes in theirpharmacology. Subtle structural changes identified as molecular switches might modulate the functional activity of allosteric ligands. Here we review these switches discovered in the metabotropic glutamate receptor family..

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| S-EPMC321022 | biostudies-other

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