Evidence map›Paper›PMID 41750392›Full record

ReviewBiomolecules2026

Glutamate Metabotropic Receptors-Linked Postsynaptic Density Proteins: An Emergent Hub for Antipsychotics' Regulation of Synaptic Plasticity and Metaplasticity.

Annarita Barone, Licia Vellucci, Anita Nasti, Benedetta Mazza, Federica Iannotta, Felice Iasevoli, Andrea de Bartolomeis

Abstract readReview
In one paragraph

Review in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Annarita BaroneSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.ORCID 0000-0002-2751-5683
Licia VellucciSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.ORCID 0000-0001-5301-405X
Anita NastiSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
Benedetta MazzaSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
Federica IannottaSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.ORCID 0000-0002-4938-7627
Felice IasevoliSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.ORCID 0000-0002-7051-5013
Andrea de BartolomeisSection of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.

Funding

National Recovery and Resilience Plan PNRR-MCTN2-2023-12378276National Recovery and Resilience Plan project MNESYS (PE0000006)
6 · The paper itself

Abstract

Glutamate metabotropic receptors (mGluRs) and their molecular partners at the postsynaptic density (PSD) represent a highly dynamic molecular hub that integrates multiple neurotransmitter signals and regulates synaptic plasticity and metaplasticity, which are putatively involved in the pathophysiology of psychiatric illnesses, including schizophrenia. Group I mGluRs (mGluR1 and mGluR5) interact with PSD adaptor and scaffolding proteins, such as Homer, Shank, Norbin, and PICK1, as well as intracellular downstream effectors, creating a molecular network that resembles a Lego-like structure, where modular protein interactions fine-tune glutamatergic transmission. Evidence from preclinical research indicates that dysregulation of mGluR expression and function, along with disrupted PSD protein expression, may contribute to the pathophysiology of schizophrenia by altering glutamatergic neurotransmission and synaptic stability. Antipsychotic mechanisms of action may involve, at least in part, the modulation of mGluR activity mediated through PSD proteins. Notably, novel agents that enhance spinogenesis by acting at the level of PSD proteins, such as SPG302, may open promising avenues for therapeutics aimed at restoring synaptic integrity. While Group I mGluRs dominate postsynaptic regulation, Group II (mGluR2/3) and III (mGluR4/6/7/8) receptors -primarily presynaptic- inhibit neurotransmitter release and plasticity, offering complementary therapeutic avenues. Emerging strategies, such as allosteric modulators of mGluRs, aim to rebalance synaptic signaling in treatment-resistant schizophrenia. This review synthesizes how PSD proteins and mGluRs interact in schizophrenia, exploring their potential as druggable targets for novel therapies.

Indexed as

Antipsychotic AgentsNeuronal PlasticityReceptors, Metabotropic GlutamateSchizophreniaAnimalsHomer Scaffolding ProteinsHumansNerve Tissue ProteinsPost-Synaptic DensitySynaptic TransmissionAntipsychotic AgentsHomer Scaffolding ProteinsNerve Tissue Proteinspostsynaptic density proteinsReceptors, Metabotropic Glutamateantipsychoticsclozapinemetabotropic glutamate receptorspostsynaptic densitysynaptic plasticitytreatment resistant schizophrenia

Identifiers

PMID41750392
PMCPMC12938303

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.