{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:07:12Z","timestamp":1790370432531,"version":"4.1.0"},"reference-count":259,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Recovery and Resilience plan","award":["PNRR-MCTN2-2023-12378276"],"award-info":[{"award-number":["PNRR-MCTN2-2023-12378276"]}]},{"name":"Italian Ministry of University and Research","award":["MNESYS (PE0000006)"],"award-info":[{"award-number":["MNESYS (PE0000006)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom16020324","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:44:27Z","timestamp":1771501467000},"page":"324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Glutamate Metabotropic Receptors-Linked Postsynaptic Density Proteins: An Emergent Hub for Antipsychotics\u2019 Regulation of Synaptic Plasticity and Metaplasticity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2751-5683","authenticated-orcid":false,"given":"Annarita","family":"Barone","sequence":"first","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5301-405X","authenticated-orcid":false,"given":"Licia","family":"Vellucci","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Nasti","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Mazza","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4938-7627","authenticated-orcid":false,"given":"Federica","family":"Iannotta","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-5013","authenticated-orcid":false,"given":"Felice","family":"Iasevoli","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"de Bartolomeis","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Laboratory of Molecular and Translational Psychiatry, Unit of Treatment-Resistant Psychiatric Disorders, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2026, February 11). Schizophrenia. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/schizophrenia."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3371\/CSRP.4.1.5","article-title":"Dopamine D2 receptors as treatment targets in schizophrenia","volume":"4","author":"Seeman","year":"2010","journal-title":"Clin. Schizophr. Relat. Psychoses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.euroneuro.2018.03.004","article-title":"Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine","volume":"28","author":"Takaki","year":"2018","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00213-010-1954-0","article-title":"Divergent acute and chronic modulation of glutamatergic postsynaptic density genes expression by the antipsychotics haloperidol and sertindole","volume":"212","author":"Iasevoli","year":"2010","journal-title":"Psychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.euroneuro.2015.07.007","article-title":"Lurasidone and fluoxetine reduce novelty-induced hypophagia and NMDA receptor subunit and PSD-95 expression in mouse brain","volume":"25","author":"Stan","year":"2015","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/schbul\/sbp006","article-title":"The dopamine hypothesis of schizophrenia: Version III\u2014the final common pathway","volume":"35","author":"Howes","year":"2009","journal-title":"Schizophr. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1196\/annals.1300.020","article-title":"Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia","volume":"1003","author":"Coyle","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3371\/CSRP.4.3.6","article-title":"Thinking glutamatergically: Changing concepts of schizophrenia based upon changing neurochemical models","volume":"4","author":"Kantrowitz","year":"2010","journal-title":"Clin. Schizophr. Relat. Psychoses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.tips.2008.10.006","article-title":"Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia","volume":"30","author":"Conn","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"de Bartolomeis, A., Vellucci, L., De Simone, G., Mazza, B., Barone, A., and Ciccarelli, M. (2023). Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics\u2019 Treatment of Schizophrenia. Cells, 12.","DOI":"10.3390\/cells12040574"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109782","DOI":"10.1016\/j.cellsig.2020.109782","article-title":"Molecular architecture of postsynaptic Interactomes","volume":"76","author":"Wilkinson","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nicoletti, F., Orlando, R., Di Menna, L., Cannella, M., Notartomaso, S., Mascio, G., Iacovelli, L., Matrisciano, F., Fazio, F., and Caraci, F. (2019). Targeting mGlu Receptors for Optimization of Antipsychotic Activity and Disease\u2014Modifying Effect in Schizophrenia. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00049"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"ra5","DOI":"10.1126\/scisignal.aab0467","article-title":"Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia","volume":"9","author":"Moreno","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_14","unstructured":"Spinogenix, Inc. (2026, February 11). Study of SPG302 in Adults with Schizophrenia, Available online: https:\/\/www.clinicaltrials.gov\/study\/NCT06442462."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.bbadis.2015.12.007","article-title":"Hexa (ethylene glycol) derivative of benzothiazole aniline promotes dendritic spine formation through the RasGRF1-Ras dependent pathway","volume":"1862","author":"Lee","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1126\/science.7569905","article-title":"Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95","volume":"269","author":"Kornau","year":"1995","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1176\/appi.ajp.2016.16050503","article-title":"Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology","volume":"174","author":"Howes","year":"2017","journal-title":"Am. J. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.4088\/JCP.18com12123","article-title":"Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia","volume":"80","author":"Kane","year":"2019","journal-title":"J. Clin. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.pnpbp.2017.09.002","article-title":"Treatment resistant schizophrenia and neurological soft signs may converge on the same pathology: Evidence from explanatory analysis on clinical, psychopathological, and cognitive variables","volume":"81","author":"Prinzivalli","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.jpsychires.2022.09.044","article-title":"Disorganization domain as a putative predictor of Treatment Resistant Schizophrenia (TRS) diagnosis: A machine learning approach","volume":"155","author":"Barone","year":"2022","journal-title":"J. Psychiatr. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.2147\/NDT.S47571","article-title":"Tobacco smoking in treatment-resistant schizophrenia patients is associated with impaired cognitive functioning, more severe negative symptoms, and poorer social adjustment","volume":"9","author":"Iasevoli","year":"2013","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41537-024-00535-4","article-title":"Addressing brain metabolic connectivity in treatment-resistant schizophrenia: A novel graph theory-driven application of (18)F-FDG-PET with antipsychotic dose correction","volume":"10","author":"Iasevoli","year":"2024","journal-title":"Schizophrenia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"173446","DOI":"10.1016\/j.pbb.2022.173446","article-title":"Clinical investigations of compounds targeting metabotropic glutamate receptors","volume":"219","author":"Witkin","year":"2022","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108275","DOI":"10.1016\/j.pharmthera.2022.108275","article-title":"Targeting mGluR2\/3 for treatment of neurodegenerative and neuropsychiatric diseases","volume":"239","author":"Li","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1146\/annurev.pharmtox.37.1.205","article-title":"Pharmacology and functions of metabotropic glutamate receptors","volume":"37","author":"Conn","year":"1997","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic glutamate receptors: Physiology, pharmacology, and disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0896-6273(04)00013-3","article-title":"Synaptic activation of metabotropic glutamate receptors regulates dendritic outputs of thalamic interneurons","volume":"41","author":"Govindaiah","year":"2004","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/0166-2236(88)90183-X","article-title":"A new mechanism for glutamate receptor action: Phosphoinositide hydrolysis","volume":"11","author":"Sladeczek","year":"1988","journal-title":"Trends Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1073\/pnas.83.6.1931","article-title":"Excitatory amino acid recognition sites coupled with inositol phospholipid metabolism: Developmental changes and interaction with alpha 1-adrenoceptors","volume":"83","author":"Nicoletti","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/325531a0","article-title":"A new type of glutamate receptor linked to inositol phospholipid metabolism","volume":"325","author":"Sugiyama","year":"1987","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0896-6273(89)90121-9","article-title":"Glutamate receptor subtypes may be classified into two major categories: A study on Xenopus oocytes injected with rat brain mRNA","volume":"3","author":"Sugiyama","year":"1989","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/349760a0","article-title":"Sequence and expression of a metabotropic glutamate receptor","volume":"349","author":"Masu","year":"1991","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0896-6273(93)90269-W","article-title":"The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins","volume":"11","author":"Sheppard","year":"1993","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/aps.2011.186","article-title":"Structure and ligand recognition of class C GPCRs","volume":"33","author":"Chun","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/35039564","article-title":"Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor","volume":"407","author":"Kunishima","year":"2000","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1073\/pnas.052708599","article-title":"Structural views of the ligand-binding cores of a metabotropic glutamate receptor complexed with an antagonist and both glutamate and Gd3+","volume":"99","author":"Tsuchiya","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1152\/jn.1995.74.1.122","article-title":"Roles of specific metabotropic glutamate receptor subtypes in regulation of hippocampal CA1 pyramidal cell excitability","volume":"74","author":"Gereau","year":"1995","journal-title":"J. Neurophysiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0028-3908(94)00149-M","article-title":"Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4","volume":"34","author":"Flor","year":"1995","journal-title":"Neuropharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jnr.21437","article-title":"Metabotropic glutamate receptors: Phosphorylation and receptor signaling","volume":"86","author":"Kim","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1111\/j.1460-9568.1996.tb01611.x","article-title":"Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus","volume":"8","author":"Lujan","year":"1996","journal-title":"Eur. J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0891-0618(97)00051-3","article-title":"Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites","volume":"13","author":"Roberts","year":"1997","journal-title":"J. Chem. Neuroanat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0896-6273(92)90165-A","article-title":"Cellular localization of a metabotropic glutamate receptor in rat brain","volume":"9","author":"Martin","year":"1992","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0304-3940(93)90227-C","article-title":"Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain","volume":"163","author":"Shigemoto","year":"1993","journal-title":"Neurosci. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7503","DOI":"10.1523\/JNEUROSCI.17-19-07503.1997","article-title":"Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus","volume":"17","author":"Shigemoto","year":"1997","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0028-3908(98)00222-6","article-title":"Induction of LTD in the adult hippocampus by the synaptic activation of AMPA\/kainate and metabotropic glutamate receptors","volume":"38","author":"Kemp","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/366687a0","article-title":"Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb","volume":"366","author":"Hayashi","year":"1993","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/0306-4522(96)00316-8","article-title":"Metabotropic glutamate receptors mGluR2 and mGluR5 are expressed in two non-overlapping populations of Golgi cells in the rat cerebellum","volume":"75","author":"Neki","year":"1996","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0304-3940(95)12248-6","article-title":"Pre- and postsynaptic localization of a metabotropic glutamate receptor, mGluR2, in the rat brain: An immunohistochemical study with a monoclonal antibody","volume":"202","author":"Neki","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1523\/JNEUROSCI.19-13-05173.1999","article-title":"Distinct subtypes of metabotropic glutamate receptors mediate differential actions on excitability of spinal respiratory motoneurons","volume":"19","author":"Dong","year":"1999","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1523\/JNEUROSCI.16-06-02044.1996","article-title":"Immunocytochemical localization of group III metabotropic glutamate receptors in the hippocampus with subtype-specific antibodies","volume":"16","author":"Bradley","year":"1996","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1046\/j.1471-4159.1998.71020636.x","article-title":"Distribution and developmental regulation of metabotropic glutamate receptor 7a in rat brain","volume":"71","author":"Bradley","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/381523a0","article-title":"Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone","volume":"381","author":"Shigemoto","year":"1996","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0306-4522(01)00591-7","article-title":"Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS","volume":"110","author":"Corti","year":"2002","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0092-8674(94)90151-1","article-title":"Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells","volume":"77","author":"Nomura","year":"1994","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/cne.903600402","article-title":"Distributions of the mRNAs for L-2-amino-4-phosphonobutyrate-sensitive metabotropic glutamate receptors, mGluR4 and mGluR7, in the rat brain","volume":"360","author":"Ohishi","year":"1995","journal-title":"J. Comp. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev.pharmtox.48.113006.094830","article-title":"Regulation of GPCRs by endocytic membrane trafficking and its potential implications","volume":"48","author":"Hanyaloglu","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1124\/mol.60.6.1243","article-title":"Agonist-stimulated and tonic internalization of metabotropic glutamate receptor 1a in human embryonic kidney 293 cells: Agonist-stimulated endocytosis is beta-arrestin1 isoform-specific","volume":"60","author":"Dale","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1046\/j.1471-4159.2001.00421.x","article-title":"Agonist-induced internalization of the metabotropic glutamate receptor 1a is arrestin- and dynamin-dependent","volume":"78","author":"Mundell","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0031-6997(24)01478-9","article-title":"Evolving concepts in G protein-coupled receptor endocytosis: The role in receptor desensitization and signaling","volume":"53","author":"Ferguson","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S379","DOI":"10.1038\/sj.bjp.0707604","article-title":"Agonist-selective mechanisms of GPCR desensitization","volume":"153","author":"Kelly","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.pharmtox.38.1.289","article-title":"The role of receptor kinases and arrestins in G protein-coupled receptor regulation","volume":"38","author":"Krupnick","year":"1998","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.biocel.2016.03.003","article-title":"Inside story of Group I Metabotropic Glutamate Receptors (mGluRs)","volume":"77","author":"Bhattacharyya","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.pharmthera.2005.01.008","article-title":"Regulation of metabotropic glutamate receptor signaling, desensitization and endocytosis","volume":"111","author":"Dhami","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6185","DOI":"10.1073\/pnas.97.11.6185","article-title":"Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: Selective desensitization of the inositol trisphosphate\/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain","volume":"97","author":"Francesconi","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0896-6273(00)80442-0","article-title":"Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5","volume":"20","author":"Gereau","year":"1998","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-981-13-3065-0_12","article-title":"Group I Metabotropic Glutamate Receptors (mGluRs): Ins and Outs","volume":"1112","author":"Mahato","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1523\/JNEUROSCI.0026-21.2021","article-title":"The Complex Formed by Group I Metabotropic Glutamate Receptor (mGluR) and Homer1a Plays a Central Role in Metaplasticity and Homeostatic Synaptic Scaling","volume":"41","author":"Bockaert","year":"2021","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/386284a0","article-title":"Homer: A protein that selectively binds metabotropic glutamate receptors","volume":"386","author":"Brakeman","year":"1997","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23969","DOI":"10.1074\/jbc.273.37.23969","article-title":"Novel members of the Vesl\/Homer family of PDZ proteins that bind metabotropic glutamate receptors","volume":"273","author":"Kato","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0896-6273(00)80589-9","article-title":"Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors","volume":"21","author":"Tu","year":"1998","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0896-6273(00)80588-7","article-title":"Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins","volume":"21","author":"Xiao","year":"1998","journal-title":"Neuron"},{"key":"ref_72","first-page":"re8","article-title":"Homer as both a scaffold and transduction molecule","volume":"2002","author":"Fagni","year":"2002","journal-title":"Sci. STKE Signal Transduct. Knowl. Environ."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"de Bartolomeis, A., Manchia, M., Marmo, F., Vellucci, L., Iasevoli, F., and Barone, A. (2020). Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.00369"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"de Bartolomeis, A., De Simone, G., Ciccarelli, M., Castiello, A., Mazza, B., Vellucci, L., and Barone, A. (2022). Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123183"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"104596","DOI":"10.1016\/j.neubiorev.2022.104596","article-title":"The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular \u201cLego\u201d in the pathophysiology of psychiatric disorders. A systematic review and translational insight","volume":"136","author":"Barone","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"de Bartolomeis, A., Ciccarelli, M., De Simone, G., Mazza, B., Barone, A., and Vellucci, L. (2023). Canonical and Non-Canonical Antipsychotics\u2019 Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065945"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/gb-2007-8-2-206","article-title":"The Homer family proteins","volume":"8","author":"Furuichi","year":"2007","journal-title":"Genome Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/S0022-2836(02)00170-5","article-title":"Crystal structure of the Homer 1 family conserved region reveals the interaction between the EVH1 domain and own proline-rich motif","volume":"318","author":"Irie","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8560","DOI":"10.1523\/JNEUROSCI.1830-08.2008","article-title":"Endogenous homer proteins regulate metabotropic glutamate receptor signaling in neurons","volume":"28","author":"Kammermeier","year":"2008","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7238","DOI":"10.1523\/JNEUROSCI.20-19-07238.2000","article-title":"Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels","volume":"20","author":"Kammermeier","year":"2000","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"25953","DOI":"10.1074\/jbc.274.36.25953","article-title":"Homer 1b regulates the trafficking of group I metabotropic glutamate receptors","volume":"274","author":"Roche","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13801","DOI":"10.1073\/pnas.96.24.13801","article-title":"Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c\/vesl-1L) in group 1 metabotropic glutamate receptor clustering","volume":"96","author":"Tadokoro","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"16022","DOI":"10.1038\/npjschz.2016.22","article-title":"Molecular evidence of synaptic pathology in the CA1 region in schizophrenia","volume":"2","author":"Matosin","year":"2016","journal-title":"NPJ Schizophr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.schres.2015.05.001","article-title":"Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia","volume":"166","author":"Matosin","year":"2015","journal-title":"Schizophr. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1007\/s11357-012-9479-6","article-title":"Homer-1a immediate early gene expression correlates with better cognitive performance in aging","volume":"35","author":"Kaja","year":"2013","journal-title":"Age"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6327","DOI":"10.1523\/JNEUROSCI.23-15-06327.2003","article-title":"Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a","volume":"23","author":"Sala","year":"2003","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"109725","DOI":"10.1016\/j.pnpbp.2019.109725","article-title":"Glutamatergic postsynaptic density in early life stress programming: Topographic gene expression of mGlu5 receptors and Homer proteins","volume":"96","author":"Buonaguro","year":"2020","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7575","DOI":"10.1523\/JNEUROSCI.5083-05.2006","article-title":"Visual experience regulates metabotropic glutamate receptor-mediated plasticity of AMPA receptor synaptic transmission by homer1a induction","volume":"26","author":"Cline","year":"2006","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/s41467-017-01191-2","article-title":"Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice","volume":"8","author":"Aloisi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41467-022-35680-w","article-title":"mGluR5 is transiently confined in perisynaptic nanodomains to shape synaptic function","volume":"14","author":"Scheefhals","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1523\/JNEUROSCI.22-10-03910.2002","article-title":"Receptor activation and homer differentially control the lateral mobility of metabotropic glutamate receptor 5 in the neuronal membrane","volume":"22","author":"Fourgeaud","year":"2002","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.neuron.2010.01.016","article-title":"Group 1 mGluR-dependent synaptic long-term depression: Mechanisms and implications for circuitry and disease","volume":"65","author":"Huber","year":"2010","journal-title":"Neuron"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0896-6273(00)80810-7","article-title":"Coupling of mGluR\/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins","volume":"23","author":"Tu","year":"1999","journal-title":"Neuron"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1523\/JNEUROSCI.17-15-05687.1997","article-title":"Characterization of guanylate kinase-associated protein, a postsynaptic density protein at excitatory synapses that interacts directly with postsynaptic density-95\/synapse-associated protein 90","volume":"17","author":"Naisbitt","year":"1997","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1152\/jn.1998.80.1.143","article-title":"Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor function at the developing corticothalamic synapse","volume":"80","author":"Golshani","year":"1998","journal-title":"J. Neurophysiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/j.1469-7793.1998.761bg.x","article-title":"Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus","volume":"511","author":"Otani","year":"1998","journal-title":"J. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0014-2999(91)90921-C","article-title":"Selective activation of quisqualate metabotropic receptor potentiates NMDA but not AMPA responses","volume":"205","author":"Aniksztejn","year":"1991","journal-title":"Eur. J. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0896-6273(00)80683-2","article-title":"Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines","volume":"22","author":"Emptage","year":"1999","journal-title":"Neuron"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0896-6273(00)80698-4","article-title":"Synaptic [Ca2+]: Intracellular stores spill their guts","volume":"22","author":"Svoboda","year":"1999","journal-title":"Neuron"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/363347a0","article-title":"Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors","volume":"363","author":"Bashir","year":"1993","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/368740a0","article-title":"A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation","volume":"368","author":"Bortolotto","year":"1994","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1152\/jn.1995.74.3.1075","article-title":"Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation","volume":"74","author":"Selig","year":"1995","journal-title":"J. Neurophysiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0092-8674(94)90204-6","article-title":"Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice","volume":"79","author":"Aiba","year":"1994","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1523\/JNEUROSCI.17-13-05196.1997","article-title":"Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP","volume":"17","author":"Lu","year":"1997","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/372237a0","article-title":"Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1","volume":"372","author":"Conquet","year":"1994","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"111032","DOI":"10.1016\/j.pnpbp.2024.111032","article-title":"Perinatal stress modulates glutamatergic functional connectivity: A post-synaptic density immediate early gene-based network analysis","volume":"133","author":"Vellucci","year":"2024","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Iasevoli, F., Buonaguro, E.F., Avagliano, C., Barone, A., Eramo, A., Vellucci, L., and de Bartolomeis, A. (2020). The Effects of Antipsychotics on the Synaptic Plasticity Gene Homer1a Depend on a Combination of Their Receptor Profile, Dose, Duration of Treatment, and Brain Regions Targeted. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155555"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1177\/0269881116658987","article-title":"Postsynaptic density protein transcripts are differentially modulated by minocycline alone or in add-on to haloperidol: Implications for treatment resistant schizophrenia","volume":"31","author":"Buonaguro","year":"2017","journal-title":"J. Psychopharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.euroneuro.2015.01.003","article-title":"Progressive recruitment of cortical and striatal regions by inducible postsynaptic density transcripts after increasing doses of antipsychotics with different receptor profiles: Insights for psychosis treatment","volume":"25","author":"Iasevoli","year":"2015","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1113\/JP284004","article-title":"Novel regenerative drug, SPG302 promotes functional recovery of diaphragm muscle activity after cervical spinal cord injury","volume":"601","author":"Fogarty","year":"2023","journal-title":"J. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0928-4257(97)87901-6","article-title":"Expression mechanisms of long-term potentiation in the hippocampus","volume":"90","author":"Isaac","year":"1996","journal-title":"J. Physiol. Paris"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4363","DOI":"10.1073\/pnas.89.10.4363","article-title":"Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade","volume":"89","author":"Dudek","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1016\/0024-3205(80)90509-3","article-title":"The effects of repetitive low frequency stimulation on control and \u201cpotentiated\u201d synaptic responses in the hippocampus","volume":"27","author":"Barrionuevo","year":"1980","journal-title":"Life Sci."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Chater, T.E., and Goda, Y. (2014). The role of AMPA receptors in postsynaptic mechanisms of synaptic plasticity. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00401"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.conb.2011.12.006","article-title":"Regulation of AMPA receptor trafficking and synaptic plasticity","volume":"22","author":"Anggono","year":"2012","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.neuron.2013.10.025","article-title":"AMPARs and synaptic plasticity: The last 25 years","volume":"80","author":"Huganir","year":"2013","journal-title":"Neuron"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S0166-2236(02)02270-1","article-title":"Regulation of AMPA receptors during synaptic plasticity","volume":"25","author":"Song","year":"2002","journal-title":"Trends Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0896-6273(03)00640-8","article-title":"AMPA receptor trafficking at excitatory synapses","volume":"40","author":"Bredt","year":"2003","journal-title":"Neuron"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Park, M. (2018). AMPA Receptor Trafficking for Postsynaptic Potentiation. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00361"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e48037","DOI":"10.15252\/embr.201948037","article-title":"Distinct regulation of bioenergetics and translation by group I mGluR and NMDAR","volume":"21","author":"Chakraborty","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00232-024-00326-z","article-title":"Postsynaptic Density Proteins and Their Role in the Trafficking of Group I Metabotropic Glutamate Receptors","volume":"257","author":"Aruna","year":"2024","journal-title":"J. Membr. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8575","DOI":"10.1074\/jbc.RA119.011979","article-title":"The post-synaptic scaffolding protein tamalin regulates ligand-mediated trafficking of metabotropic glutamate receptors","volume":"295","author":"Pandey","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1523\/JNEUROSCI.1037-21.2021","article-title":"Regulation of Metabotropic Glutamate Receptor Internalization and Synaptic AMPA Receptor Endocytosis by the Postsynaptic Protein Norbin","volume":"42","author":"Ojha","year":"2022","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1124\/pr.109.001735","article-title":"Metabotropic glutamate receptor-mediated long-term depression: Molecular mechanisms","volume":"61","author":"Gladding","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.pain.2005.08.004","article-title":"Signal transduction pathways of group I metabotropic glutamate receptor-induced long-term depression at sensory spinal synapses","volume":"118","author":"Heinke","year":"2005","journal-title":"Pain"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1073\/pnas.0306156101","article-title":"Clathrin-mediated endocytosis is required for compensatory regulation of GLR-1 glutamate receptors after activity blockade","volume":"101","author":"Grunwald","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/35072500","article-title":"Role of AMPA receptor endocytosis in synaptic plasticity","volume":"2","author":"Carroll","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev-neuro-080317-062155","article-title":"Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease","volume":"41","author":"Monday","year":"2018","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"a005736","DOI":"10.1101\/cshperspect.a005736","article-title":"Homeostatic synaptic plasticity: Local and global mechanisms for stabilizing neuronal function","volume":"4","author":"Turrigiano","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"10892","DOI":"10.3390\/ijms150610892","article-title":"Activation of mGluR5 attenuates NMDA-induced neurotoxicity through disruption of the NMDAR-PSD-95 complex and preservation of mitochondrial function in differentiated PC12 cells","volume":"15","author":"Dai","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1523\/JNEUROSCI.02-01-00032.1982","article-title":"Theory for the development of neuron selectivity: Orientation specificity and binocular interaction in visual cortex","volume":"2","author":"Bienenstock","year":"1982","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S0166-2236(96)80018-X","article-title":"Metaplasticity: The plasticity of synaptic plasticity","volume":"19","author":"Abraham","year":"1996","journal-title":"Trends Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1038\/s41598-018-22768-x","article-title":"Physiological activation of mGlu5 receptors supports the ion channel function of NMDA receptors in hippocampal LTD induction in vivo","volume":"8","author":"Hu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s12035-011-8187-z","article-title":"mGluRs modulate strength and timing of excitatory transmission in hippocampal area CA3","volume":"44","author":"Cosgrove","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1460-9568.2004.03511.x","article-title":"Stimulation of N-methyl-D-aspartate receptors, AMPA receptors or metabotropic glutamate receptors leads to rapid internalization of AMPA receptors in cultured nucleus accumbens neurons","volume":"20","author":"Mangiavacchi","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.conb.2009.03.011","article-title":"Protein translation in synaptic plasticity: mGluR-LTD, Fragile X","volume":"19","author":"Waung","year":"2009","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1523\/JNEUROSCI.22-13-05452.2002","article-title":"Metabotropic glutamate receptor 1-induced upregulation of NMDA receptor current: Mediation through the Pyk2\/Src-family kinase pathway in cortical neurons","volume":"22","author":"Heidinger","year":"2002","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/j.1365-2826.2010.02020.x","article-title":"Metabotropic glutamate receptors: Gatekeepers of homeostasis","volume":"22","author":"Kuzmiski","year":"2010","journal-title":"J. Neuroendocr."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1152\/physrev.1998.78.1.143","article-title":"Retrograde signaling in the development and modification of synapses","volume":"78","author":"Fitzsimonds","year":"1998","journal-title":"Physiol. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrn2867","article-title":"Long-term depression in the CNS","volume":"11","author":"Collingridge","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1176\/appi.ajp.2010.10030318","article-title":"Alterations in metabotropic glutamate receptor 1\u03b1 and regulator of G protein signaling 4 in the prefrontal cortex in schizophrenia","volume":"167","author":"Volk","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/syn.20164","article-title":"Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia","volume":"57","author":"Gupta","year":"2005","journal-title":"Synapse"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"eabn7357","DOI":"10.1126\/sciadv.abn7357","article-title":"Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission","volume":"8","author":"Liang","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nature06612","article-title":"Identification of a serotonin\/glutamate receptor complex implicated in psychosis","volume":"452","author":"Ang","year":"2008","journal-title":"Nature"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.schres.2011.01.008","article-title":"Density of metabotropic glutamate receptors 2 and 3 (mGluR2\/3) in the dorsolateral prefrontal cortex does not differ with schizophrenia diagnosis but decreases with age","volume":"128","author":"Frank","year":"2011","journal-title":"Schizophr. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1503\/jpn.130242","article-title":"Metabotropic glutamate receptor mGluR2\/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: Implications for novel mGluR-based therapeutics","volume":"39","author":"Matosin","year":"2014","journal-title":"J. Psychiatry Neurosci. JPN"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.gep.2016.10.001","article-title":"Developmental expression of mGlu2 and mGlu3 in the mouse brain","volume":"22","author":"McOmish","year":"2016","journal-title":"Gene Expr. Patterns GEP"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1523\/JNEUROSCI.2331-12.2013","article-title":"Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: Role of maternal immune system","volume":"33","author":"Holloway","year":"2013","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neuropharm.2015.08.003","article-title":"Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment","volume":"115","author":"Matosin","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"277","DOI":"10.5498\/wjp.v11.i7.277","article-title":"Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets","volume":"11","year":"2021","journal-title":"World J. Psychiatry"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41398-020-0763-4","article-title":"Variants of GRM7 as risk factor and response to antipsychotic therapy in schizophrenia","volume":"10","author":"Liang","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0168-0102(03)00162-7","article-title":"Cooperativity between activation of metabotropic glutamate receptors and NMDA receptors in the induction of LTP in hippocampal CA1 neurons","volume":"46","author":"Fujii","year":"2003","journal-title":"Neurosci. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"12604","DOI":"10.1073\/pnas.0405077101","article-title":"Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia","volume":"101","author":"Egan","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.schres.2004.07.002","article-title":"A case-control study of the relationship between the metabotropic glutamate receptor 3 gene and schizophrenia in the Chinese population","volume":"73","author":"Chen","year":"2005","journal-title":"Schizophr. Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1038\/sj.npp.1301669","article-title":"Expression of a GRM3 splice variant is increased in the dorsolateral prefrontal cortex of individuals carrying a schizophrenia risk SNP","volume":"33","author":"Sartorius","year":"2008","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.neubiorev.2010.01.002","article-title":"Genetic association studies of glutamate, GABA and related genes in schizophrenia and bipolar disorder: A decade of advance","volume":"34","author":"Cherlyn","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511, 421\u2013427.","DOI":"10.1038\/nature13595"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ajmg.1622","article-title":"Human metabotropic glutamate receptor 2 gene (GRM2): Chromosomal sublocalization (3p21.1-p21.2) and genomic organization","volume":"114","author":"Cichon","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.schres.2005.04.001","article-title":"Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment","volume":"77","author":"Bishop","year":"2005","journal-title":"Schizophr. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature12929","article-title":"De novo mutations in schizophrenia implicate synaptic networks","volume":"506","author":"Fromer","year":"2014","journal-title":"Nature"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1038\/s41380-023-01991-7","article-title":"Variability and magnitude of brain glutamate levels in schizophrenia: A meta and mega-analysis","volume":"28","author":"Merritt","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.euroneuro.2012.11.014","article-title":"Imaging brain gene expression profiles by antipsychotics: Region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol","volume":"23","author":"Marmo","year":"2013","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s40263-015-0278-3","article-title":"Update on the Mechanism of Action of Aripiprazole: Translational Insights into Antipsychotic Strategies Beyond Dopamine Receptor Antagonism","volume":"29","author":"Tomasetti","year":"2015","journal-title":"CNS Drugs"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/jnr.23713","article-title":"Dopamine D2 receptors are involved in the regulation of Fyn and metabotropic glutamate receptor 5 phosphorylation in the rat striatum in vivo","volume":"94","author":"Mao","year":"2016","journal-title":"J. Neurosci. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.cell.2013.07.001","article-title":"A prolyl-isomerase mediates dopamine-dependent plasticity and cocaine motor sensitization","volume":"154","author":"Park","year":"2013","journal-title":"Cell"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1111\/j.1460-9568.2007.05710.x","article-title":"D1- and D2-like dopamine receptors regulate signaling properties of group I metabotropic glutamate receptors in the rat globus pallidus","volume":"26","author":"Poisik","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.psychres.2017.11.048","article-title":"Effects of short- and long-term aripiprazole treatment on Group I mGluRs in the nucleus accumbens: Comparison with haloperidol","volume":"260","author":"Lum","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1124\/jpet.106.110684","article-title":"Habituation deficits induced by metabotropic glutamate receptors 2\/3 receptor blockade in mice: Reversal by antipsychotic drugs","volume":"320","author":"Bespalov","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41398-024-02832-z","article-title":"Effect of antipsychotic drugs on group II metabotropic glutamate receptor expression and epigenetic control in postmortem brains of schizophrenia subjects","volume":"14","author":"Rivero","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/nn.3181","article-title":"HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity","volume":"15","author":"Kurita","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1038\/nn.4616","article-title":"Antipsychotic-induced Hdac2 transcription via NF-\u03baB leads to synaptic and cognitive side effects","volume":"20","author":"Ibi","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Fukuyama, K., Kato, R., Murata, M., Shiroyama, T., and Okada, M. (2019). Clozapine Normalizes a Glutamatergic Transmission Abnormality Induced by an Impaired NMDA Receptor in the Thalamocortical Pathway via the Activation of a Group III Metabotropic Glutamate Receptor. Biomolecules, 9.","DOI":"10.3390\/biom9060234"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1111\/bph.70112","article-title":"Exploring the pathophysiology underlying clozapine-induced enhancement of glutamatergic transmission through L-glutamate and D-serine release associated with pannexin1 hemichannels","volume":"182","author":"Okada","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Fukuyama, K., Motomura, E., and Okada, M. (2023). Enhanced L-\u03b2-Aminoisobutyric Acid Is Involved in the Pathophysiology of Effectiveness for Treatment-Resistant Schizophrenia and Adverse Reactions of Clozapine. Biomolecules, 13.","DOI":"10.3390\/biom13050862"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"He, J., Li, J., Wei, Y., He, Z., Liu, J., Yuan, N., Zhou, R., He, X., Ren, H., and Gu, L. (2024). Multiple serum anti-glutamate receptor antibody levels in clozapine-treated\/na\u00efve patients with treatment-resistant schizophrenia. BMC Psychiatry, 24.","DOI":"10.1186\/s12888-024-05689-0"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1001\/archpsyc.1995.03950240016004","article-title":"Glutamate receptor dysfunction and schizophrenia","volume":"52","author":"Olney","year":"1995","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Polonchuk, L. (2012). Toward a New Gold Standard for Early Safety: Automated Temperature-Controlled hERG Test on the PatchLiner. Front. Pharmacol., 3.","DOI":"10.3389\/fphar.2012.00003"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"44301","DOI":"10.1074\/jbc.M112.413161","article-title":"Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A\u00b7mGlu2) receptor heteromerization and its psychoactive behavioral function","volume":"287","author":"Moreno","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0168-0102(97)00120-X","article-title":"Distribution of a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat and mouse: An immunohistochemical study with a monoclonal antibody","volume":"30","author":"Ohishi","year":"1998","journal-title":"Neurosci. Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.cell.2011.09.055","article-title":"Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs","volume":"147","author":"Fribourg","year":"2011","journal-title":"Cell"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/157015907781695900","article-title":"Allosteric modulators for mGlu receptors","volume":"5","author":"Gasparini","year":"2007","journal-title":"Curr. Neuropharmacol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"108886","DOI":"10.1016\/j.neuropharm.2021.108886","article-title":"Metabotropic glutamate receptor orthosteric ligands and their binding sites","volume":"204","author":"Acher","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1021\/ml400338f","article-title":"Qualification of LSP1-2111 as a Brain Penetrant Group III Metabotropic Glutamate Receptor Orthosteric Agonist","volume":"5","author":"Cajina","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1124\/dmd.116.071118","article-title":"In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2\/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1","volume":"45","author":"Pak","year":"2017","journal-title":"Drug Metab. Dispos."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/nm1632","article-title":"Activation of mGlu2\/3 receptors as a new approach to treat schizophrenia: A randomized Phase 2 clinical trial","volume":"13","author":"Patil","year":"2007","journal-title":"Nat. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1124\/dmd.114.062893","article-title":"In vitro characterization of the bioconversion of pomaglumetad methionil, a novel metabotropic glutamate 2\/3 receptor agonist peptide prodrug","volume":"43","author":"Moulton","year":"2015","journal-title":"Drug Metab. Dispos."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tins.2015.06.002","article-title":"Positive allosteric modulators of metabotropic glutamate 2 receptors in schizophrenia treatment","volume":"38","author":"Ellaithy","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/B978-0-12-394587-7.00002-6","article-title":"Pharmacology of metabotropic glutamate receptor allosteric modulators: Structural basis and therapeutic potential for CNS disorders","volume":"115","author":"Gregory","year":"2013","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1124\/pr.114.008862","article-title":"International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: Recommendations for the nomenclature of receptor allosterism and allosteric ligands","volume":"66","author":"Christopoulos","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.tips.2012.09.001","article-title":"Ligand properties and behaviours in an allosteric age","volume":"33","author":"Langmead","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1042\/BST0320881","article-title":"Allosteric modulators of metabotropic glutamate receptors: Lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists","volume":"32","author":"Johnson","year":"2004","journal-title":"Biochem. Soc. Trans."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd2760","article-title":"Allosteric modulators of GPCRs: A novel approach for the treatment of CNS disorders","volume":"8","author":"Conn","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1124\/mol.114.094342","article-title":"Advances in G protein-coupled receptor allostery: From function to structure","volume":"86","author":"Christopoulos","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/j.cellsig.2014.04.022","article-title":"Progress toward advanced understanding of metabotropic glutamate receptors: Structure, signaling and therapeutic indications","volume":"26","author":"Yin","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/ci700257y","article-title":"Computation of octanol-water partition coefficients by guiding an additive model with knowledge","volume":"47","author":"Cheng","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1016\/j.bmcl.2010.11.119","article-title":"Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists","volume":"21","author":"Lamb","year":"2011","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1016\/j.bmcl.2012.04.112","article-title":"Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM","volume":"22","author":"Sheffler","year":"2012","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1021\/ml100181a","article-title":"Discovery of N-Aryl Piperazines as Selective mGlu(5) Potentiators with Efficacy in a Rodent Model Predictive of Anti-Psychotic Activity","volume":"1","author":"Zhou","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.coph.2014.12.002","article-title":"Metabotropic glutamate receptors as drug targets: What\u2019s new?","volume":"20","author":"Nicoletti","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.coph.2016.10.007","article-title":"Neurobiological insights and novel therapeutic opportunities for CNS disorders from mGlu receptor allosteric and biased modulation","volume":"32","author":"Hellyer","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1042\/CS20180374","article-title":"Biased agonism and allosteric modulation of metabotropic glutamate receptor 5","volume":"132","author":"Trinh","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neuropharm.2005.01.027","article-title":"mGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition","volume":"49","author":"Pietraszek","year":"2005","journal-title":"Neuropharmacology"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"173593","DOI":"10.1016\/j.pbb.2023.173593","article-title":"Group I mGluRs positive allosteric modulators improved schizophrenia-related behavioral and molecular deficits in the Poly I:C rat model","volume":"229","author":"Taskiran","year":"2023","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0304-3940(02)01261-2","article-title":"Different roles of group I and group II metabotropic glutamate receptors on phencyclidine-induced dopamine release in the rat prefrontal cortex","volume":"336","author":"Maeda","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00213-008-1103-1","article-title":"Attenuation of ketamine-evoked behavioral responses by mGluR5 positive modulators in mice","volume":"198","author":"Chan","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.biopsych.2006.12.003","article-title":"Positive allosteric modulation of metabotropic glutamate 5 (mGlu5) receptors reverses N-Methyl-D-aspartate antagonist-induced alteration of neuronal firing in prefrontal cortex","volume":"62","author":"Lecourtier","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1124\/jpet.104.079244","article-title":"A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models","volume":"313","author":"Kinney","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"18041","DOI":"10.1073\/pnas.0806669105","article-title":"Orbitofrontal cortex neurons as a common target for classic and glutamatergic antipsychotic drugs","volume":"105","author":"Homayoun","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1038\/sj.npp.1300417","article-title":"Functional Interaction Between NMDA and mGlu5 Receptors: Effects on Working Memory, Instrumental Learning, Motor Behaviors, and Dopamine Release","volume":"29","author":"Homayoun","year":"2004","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_210","first-page":"587","article-title":"Opposite influence of MPEP, an mGluR5 antagonist, on the locomotor hyperactivity induced by PCP and amphetamine","volume":"55","author":"Pietraszek","year":"2004","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s00213-004-1827-5","article-title":"The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats","volume":"175","author":"Campbell","year":"2004","journal-title":"Psychopharmacology"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.pbb.2006.05.021","article-title":"Effects of the mGluR2\/3 agonist LY379268 on ketamine-evoked behaviours and neurochemical changes in the dentate gyrus of the rat","volume":"84","author":"Imre","year":"2006","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1126\/science.281.5381.1349","article-title":"Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats","volume":"281","author":"Moghaddam","year":"1998","journal-title":"Science"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1007\/s00210-023-02587-2","article-title":"The mGluR(2\/3) orthosteric agonist LY-404,039 reduces dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset","volume":"396","author":"Kang","year":"2023","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1124\/mol.107.035170","article-title":"A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis","volume":"72","author":"Benneyworth","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0022-3565(24)35262-0","article-title":"Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex","volume":"292","author":"Marek","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1124\/jpet.105.091074","article-title":"A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2\/3 receptor agonist in mouse models predictive of antipsychotic activity","volume":"315","author":"Galici","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0014-2999(98)00526-3","article-title":"Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV","volume":"356","author":"Kilbride","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.biopsych.2007.04.016","article-title":"Phencyclidine and dizocilpine induced behaviors reduced by N-acetylaspartylglutamate peptidase inhibition via metabotropic glutamate receptors","volume":"63","author":"Olszewski","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1038\/sj.npp.1301532","article-title":"Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine","volume":"33","author":"Baker","year":"2008","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.brainres.2007.03.028","article-title":"Evaluation of the mGlu8 receptor as a putative therapeutic target in schizophrenia","volume":"1152","author":"Robbins","year":"2007","journal-title":"Brain Res."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Cie\u015blik, P., Wo\u017aniak, M., Kaczorowska, K., Bra\u0144ski, P., Burnat, G., Chocyk, A., Bobula, B., Gruca, P., Litwa, E., and Pa\u0142ucha-Poniewiera, A. (2018). Negative Allosteric Modulators of mGlu(7) Receptor as Putative Antipsychotic Drugs. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00316"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00213-004-1792-z","article-title":"Targeting metabotropic glutamate receptors for treatment of the cognitive symptoms of schizophrenia","volume":"174","author":"Moghaddam","year":"2004","journal-title":"Psychopharmacology"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00726-006-0319-9","article-title":"The role of group I metabotropic glutamate receptors in schizophrenia","volume":"32","author":"Pietraszek","year":"2007","journal-title":"Amino Acids"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"669","DOI":"10.2165\/11533230-000000000-00000","article-title":"Potential psychiatric applications of metabotropic glutamate receptor agonists and antagonists","volume":"24","author":"Krystal","year":"2010","journal-title":"CNS Drugs"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pnpbp.2015.02.012","article-title":"Perspectives on the mGluR2\/3 agonists as a therapeutic target for schizophrenia: Still promising or a dead end?","volume":"60","author":"Li","year":"2015","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.neuropharm.2004.08.018","article-title":"The mGlu2\/3 receptor agonist LY379268 injected into cortex or thalamus decreases neuronal injury in retrosplenial cortex produced by NMDA receptor antagonist MK-801: Possible implications for psychosis","volume":"47","author":"Carter","year":"2004","journal-title":"Neuropharmacology"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0022-3565(24)35084-0","article-title":"The metabotropic glutamate 2\/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats","volume":"291","author":"Cartmell","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s002130050072","article-title":"Attenuation of specific PCP-evoked behaviors by the potent mGlu2\/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine","volume":"148","author":"Cartmell","year":"2000","journal-title":"Psychopharmacology"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neuropharm.2014.05.008","article-title":"The metabotropic glutamate 2\/3 receptor agonist LY379268 counteracted ketamine-and apomorphine-induced performance deficits in the object recognition task, but not object location task, in rats","volume":"85","author":"Pitsikas","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s00213-016-4230-0","article-title":"mGluR2\/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia","volume":"233","author":"Engel","year":"2016","journal-title":"Psychopharmacology"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/jpet.106.102046","article-title":"Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice","volume":"318","author":"Galici","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1124\/jpet.108.136861","article-title":"Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2\/3 receptor agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo [3.1.0]hexane-4,6-dicarboxylic acid (LY404039)","volume":"326","author":"Fell","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/S0014-2999(00)00269-7","article-title":"Lack of effect of LY314582 (a group 2 metabotropic glutamate receptor agonist) on phencyclidine-induced locomotor activity in metabotropic glutamate receptor 2 knockout mice","volume":"397","author":"Spooren","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/cts.12566","article-title":"Population Pharmacokinetic and Exposure-dizziness Modeling for a Metabotropic Glutamate Receptor Subtype 5 Negative Allosteric Modulator in Major Depressive Disorder Patients","volume":"11","author":"Cosson","year":"2018","journal-title":"Clin. Transl. Sci."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1001\/jamapsychiatry.2016.0838","article-title":"Efficacy and Safety of Basimglurant as Adjunctive Therapy for Major Depression: A Randomized Clinical Trial","volume":"73","author":"Quiroz","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s12325-016-0468-5","article-title":"Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 Study","volume":"34","author":"Rutrick","year":"2017","journal-title":"Adv. Ther."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00213-004-1982-8","article-title":"Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects","volume":"179","author":"Krystal","year":"2005","journal-title":"Psychopharmacology"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Adams, D.H., Kinon, B.J., Baygani, S., Millen, B.A., Velona, I., Kollack-Walker, S., and Walling, D.P. (2013). A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia. BMC Psychiatry, 13.","DOI":"10.1186\/1471-244X-13-143"},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Downing, A.M., Kinon, B.J., Millen, B.A., Zhang, L., Liu, L., Morozova, M.A., Brenner, R., Rayle, T.J., Nisenbaum, L., and Zhao, F. (2014). A Double-Blind, Placebo-Controlled Comparator Study of LY2140023 monohydrate in patients with schizophrenia. BMC Psychiatry, 14.","DOI":"10.1186\/s12888-014-0351-3"},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Aboushawareb, H., Abbas, O.F., Ghabour, H., Hassan, O., Shelbaya, A.N., Abdelsalam, R., and Meshref, M. (2025). Pomgulated methionil (LY2140023) in schizophrenia patients: A systematic review and meta-analysis. BMC Psychiatry, 25.","DOI":"10.1186\/s12888-025-07199-z"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1080\/13543776.2019.1637421","article-title":"mGluR2 positive allosteric modulators: An updated patent review (2013\u20132018)","volume":"29","author":"Trabanco","year":"2019","journal-title":"Expert. Opin. Ther. Pat."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.schres.2016.02.001","article-title":"AZD8529, a positive allosteric modulator at the mGluR2 receptor, does not improve symptoms in schizophrenia: A proof of principle study","volume":"172","author":"Litman","year":"2016","journal-title":"Schizophr. Res."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1177\/0269881115573403","article-title":"Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies","volume":"29","author":"Salih","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1021\/cn400023y","article-title":"Is there a path forward for mGlu(2) positive allosteric modulators for the treatment of schizophrenia?","volume":"4","author":"Hopkins","year":"2013","journal-title":"ACS Chem. Neurosci."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/mds.28970","article-title":"A Randomized, Double-Blind, Controlled Phase II Study of Foliglurax in Parkinson\u2019s Disease","volume":"37","author":"Rascol","year":"2022","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1176\/appi.ajp.20250068","article-title":"An Update on the Use of Neuromodulation Strategies in the Treatment of Schizophrenia","volume":"182","author":"Neufeld","year":"2025","journal-title":"Am. J. Psychiatry"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/ana.24708","article-title":"Direct current stimulation induces mGluR5-dependent neocortical plasticity","volume":"80","author":"Sun","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/jnc.13931","article-title":"Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala\/piriform cortex","volume":"140","author":"Alexander","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"100339","DOI":"10.1016\/j.scog.2024.100339","article-title":"The efficacy and safety of dual-target rTMS over dorsolateral prefrontal cortex (DLPFC) and cerebellum in the treatment of negative symptoms in first-episode schizophrenia: Protocol for a multicenter, randomized, double-blind, sham-controlled study","volume":"39","author":"Wang","year":"2025","journal-title":"Schizophr. Res. Cogn."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jpsychires.2020.03.018","article-title":"Neuroprotective efficacy of different levels of high-frequency repetitive transcranial magnetic stimulation in mice with CUMS-induced depression: Involvement of the p11\/BDNF\/Homer1a signaling pathway","volume":"125","author":"Zuo","year":"2020","journal-title":"J. Psychiatr. Res."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.biopsych.2010.05.038","article-title":"Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression","volume":"68","author":"Rietschel","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1021\/cn500128b","article-title":"Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents","volume":"5","author":"Bubser","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_254","first-page":"Cd005581","article-title":"Antidepressants for the negative symptoms of schizophrenia","volume":"2006","author":"Rummel","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Stampanoni Bassi, M., Iezzi, E., Gilio, L., Centonze, D., and Buttari, F. (2019). Synaptic Plasticity Shapes Brain Connectivity: Implications for Network Topology. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246193"},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Barone, A., De Simone, G., Ciccarelli, M., Buonaguro, E.F., Tomasetti, C., Eramo, A., Vellucci, L., and de Bartolomeis, A. (2023). A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054372"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.psychres.2010.02.009","article-title":"Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions","volume":"177","author":"Iasevoli","year":"2010","journal-title":"Psychiatry Res."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/S0893-133X(02)00371-8","article-title":"Homer 1a gene expression modulation by antipsychotic drugs: Involvement of the glutamate metabotropic system and effects of D-cycloserine","volume":"27","author":"Polese","year":"2002","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s00726-016-2205-4","article-title":"D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice","volume":"48","author":"Palazzo","year":"2016","journal-title":"Amino Acids"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/324\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:55:20Z","timestamp":1771502120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":259,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["biom16020324"],"URL":"https:\/\/doi.org\/10.3390\/biom16020324","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}