General Information:

Id: 5,037
Diseases: Schizophrenia - [OMIM]
Mammalia
review
Reference: Newell KA(2013) Metabotropic glutamate receptor 5 in schizophrenia: emerging evidence for the development of antipsychotic drugs Future Med Chem 5: 1471-1474 [PMID: 24024939]

Interaction Information:

Comment The NMDAR shares a structural connection with mGluR5, via one or a combination of various scaffolding proteins (e.g., Homer, Shank, GKAP and PSD-95); through this link, mGluR5 activation enhances NMDAR activity, thereby forming the basis of mGluR5 as a novel drug target for the treatment of schizophrenia.
Formal Description
Interaction-ID: 49690

gene/protein

GRM5

increases_activity of

complex/PPI

NMDA receptor complex

via one or a combination of various scaffolding proteins (e.g., Homer, Shank, GKAP and PSD-95), if GRM5 is activated;
Drugbank entries Show/Hide entries for GRM5
Comment Homer1, a key molecule that coordinates signaling between mGluR5 and NMDAR, has reduced protein expression in the hippocampus and prefrontal cortex in schizophrenia, suggesting a possible disruption to the association between mGluR5 and the NMDAR.
Formal Description
Interaction-ID: 49691

disease

Schizophrenia

decreases_expression of

gene/protein

HOMER1

in the hippocampus and prefrontal cortex
Comment Homer1, a key molecule that coordinates signaling between mGluR5 and NMDAR, has reduced protein expression in the hippocampus and prefrontal cortex in schizophrenia, suggesting a possible disruption to the association between mGluR5 and the NMDAR.
Formal Description
Interaction-ID: 49692

gene/protein

HOMER1

affects_activity of

complex/PPI

NMDA receptor complex

concerning the coordination of signaling between mGluR5 and NMDAR;
Comment mGluR5 plays a key role in brain development, including the regulation of stem cell proliferation and migration.
Formal Description
Interaction-ID: 49693

gene/protein

GRM5

affects_activity of

Drugbank entries Show/Hide entries for GRM5
Comment mGluR5 plays a key role in brain development, including the regulation of stem cell proliferation and migration.
Formal Description
Interaction-ID: 49694

gene/protein

GRM5

affects_activity of

Drugbank entries Show/Hide entries for GRM5
Comment mGluR5 plays a key role in brain development, including the regulation of stem cell proliferation and migration.
Formal Description
Interaction-ID: 49695

gene/protein

GRM5

affects_activity of

process

regulation of stem cell migration

Drugbank entries Show/Hide entries for GRM5
Comment mGluR5 stimulates the normal developmental NMDAR NR2 subunit switch within the hippocampus, in which the ratio of NR2A-containing NMDARs compared with NR2B-containing NMDARs increases. This NR2B/NR2A subunit ‘switch’ is hypothesized to be disturbed during development in the schizophrenia brain resulting in altered NMDAR stoichiometry as well as GABA­ergic deficits.
Formal Description
Interaction-ID: 49696

gene/protein

GRM5

affects_quantity of

gene/protein

GRIN2A

in hippocampus
Drugbank entries Show/Hide entries for GRM5 or GRIN2A
Comment mGluR5 stimulates the normal developmental NMDAR NR2 subunit switch within the hippocampus, in which the ratio of NR2A-containing NMDARs compared with NR2B-containing NMDARs increases. This NR2B/NR2A subunit ‘switch’ is hypothesized to be disturbed during development in the schizophrenia brain resulting in altered NMDAR stoichiometry as well as GABA­ergic deficits.
Formal Description
Interaction-ID: 49697

gene/protein

GRM5

affects_quantity of

gene/protein

GRIN2B

in hippocampus
Drugbank entries Show/Hide entries for GRM5 or GRIN2B
Comment NR2A-containing receptors play a critical role in the development and maturation of GABAergic circuits, particularly parvalbumin-containing interneurons, which are deficient in schizophrenia.
Formal Description
Interaction-ID: 49698

gene/protein

GRIN2A

affects_activity of

Drugbank entries Show/Hide entries for GRIN2A
Comment NR2A-containing receptors play a critical role in the development and maturation of GABAergic circuits, particularly parvalbumin-containing interneurons, which are deficient in schizophrenia.
Formal Description
Interaction-ID: 49699

gene/protein

GRIN2A

affects_activity of

tissue/cell line

interneuron

Drugbank entries Show/Hide entries for GRIN2A
Comment NR2A-containing receptors play a critical role in the development and maturation of GABAergic circuits, particularly parvalbumin-containing interneurons, which are deficient in schizophrenia.
Formal Description
Interaction-ID: 49700

disease

Schizophrenia

decreases_quantity of

tissue/cell line

interneuron

Comment VU0360172, LN2463359 and LN2814617 are mGluR5 positive allosteric modulators (PAMs), a potential new class of thera­peutics for the treatment of schizophrenia. Some studies show that they are able to attenuate NMDAR antagonist-induced cognitive deficits, as well as NMDAR antagonist- and amphetamine-induced psychotomimetic effects, indicating their potential to alleviate the positive, negative and importantly the cognitive symptoms in schizophrenia patients.
Formal Description
Interaction-ID: 49701

drug/chemical compound

VU0360172

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment VU0360172, LN2463359 and LN2814617 are mGluR5 positive allosteric modulators (PAMs), a potential new class of thera­peutics for the treatment of schizophrenia. Some studies show that they are able to attenuate NMDAR antagonist-induced cognitive deficits, as well as NMDAR antagonist- and amphetamine-induced psychotomimetic effects, indicating their potential to alleviate the positive, negative and importantly the cognitive symptoms in schizophrenia patients.
Formal Description
Interaction-ID: 49702

drug/chemical compound

LN2463359

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment VU0360172, LN2463359 and LN2814617 are mGluR5 positive allosteric modulators (PAMs), a potential new class of thera­peutics for the treatment of schizophrenia. Some studies show that they are able to attenuate NMDAR antagonist-induced cognitive deficits, as well as NMDAR antagonist- and amphetamine-induced psychotomimetic effects, indicating their potential to alleviate the positive, negative and importantly the cognitive symptoms in schizophrenia patients.
Formal Description
Interaction-ID: 49703

drug/chemical compound

LN2814617

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment The mGluR5 PAM (positive allosteric modulator of mGluR5) CDPPB has been shown to reduce amphetamine-induced hyperlocomotion and prepulse inhibition deficits, presumably mediated through the dopaminergic system.
Formal Description
Interaction-ID: 49704

drug/chemical compound

CDPPB

decreases_activity of

phenotype

hyperactivity

if hyperlocomotion is amphetamine-induced;
Comment The mGluR5 PAM (positive allosteric modulator of mGluR5) CDPPB has been shown to reduce amphetamine-induced hyperlocomotion and prepulse inhibition deficits, presumably mediated through the dopaminergic system.
Formal Description
Interaction-ID: 49705

drug/chemical compound

CDPPB

decreases_activity of

Comment The dopamine D2 receptor and mGluR5 form heterodimers in the striatum, particularly at the corticostriatal glutamate synapse, suggesting a possible avenue for indirect effects of mGluR5 PAMs on striatal dopaminergic signaling.
Formal Description
Interaction-ID: 49706

gene/protein

DRD2

interacts (colocalizes) with

gene/protein

GRM5

in the striatum, particularly at the corticostriatal glutamate synapse
Drugbank entries Show/Hide entries for DRD2 or GRM5