{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:25:57Z","timestamp":1792016757883,"version":"4.4.0"},"reference-count":417,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Emerging evidence from genomics, post-mortem, and preclinical studies point to a potential dysregulation of molecular signaling at postsynaptic density (PSD) in schizophrenia pathophysiology. The PSD that identifies the archetypal asymmetric synapse is a structure of approximately 300 nm in diameter, localized behind the neuronal membrane in the glutamatergic synapse, and constituted by more than 1000 proteins, including receptors, adaptors, kinases, and scaffold proteins. Furthermore, using FASS (fluorescence-activated synaptosome sorting) techniques, glutamatergic synaptosomes were isolated at around 70 nm, where the receptors anchored to the PSD proteins can diffuse laterally along the PSD and were stabilized by scaffold proteins in nanodomains of 50\u201380 nm at a distance of 20\u201340 nm creating \u201cnanocolumns\u201d within the synaptic button. In this context, PSD was envisioned as a multimodal hub integrating multiple signaling-related intracellular functions. Dysfunctions of glutamate signaling have been postulated in schizophrenia, starting from the glutamate receptor\u2019s interaction with scaffolding proteins involved in the N-methyl-D-aspartate receptor (NMDAR). Despite the emerging role of PSD proteins in behavioral disorders, there is currently no systematic review that integrates preclinical and clinical findings addressing dysregulated PSD signaling and translational implications for antipsychotic treatment in the aberrant postsynaptic function context. Here we reviewed a critical appraisal of the role of dysregulated PSD proteins signaling in the pathophysiology of schizophrenia, discussing how antipsychotics may affect PSD structures and synaptic plasticity in brain regions relevant to psychosis.<\/jats:p>","DOI":"10.3390\/cells12040574","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T05:18:35Z","timestamp":1676006315000},"page":"574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics\u2019 Treatment of Schizophrenia"],"prefix":"10.3390","volume":"12","author":[{"given":"Andrea","family":"de Bartolomeis","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Translational Psychiatry, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"},{"name":"Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Vellucci","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Translational Psychiatry, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"},{"name":"Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0422-3415","authenticated-orcid":false,"given":"Giuseppe","family":"De Simone","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Translational Psychiatry, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"},{"name":"Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Mazza","sequence":"additional","affiliation":[{"name":"Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2751-5683","authenticated-orcid":false,"given":"Annarita","family":"Barone","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Translational Psychiatry, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"},{"name":"Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-414X","authenticated-orcid":false,"given":"Mariateresa","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Psychiatry and Translational Psychiatry, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"},{"name":"Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, University School of Medicine of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12035-012-8293-6","article-title":"Calcium-dependent networks in dopamine-glutamate interaction: The role of postsynaptic scaffolding proteins","volume":"46","author":"Tomasetti","year":"2012","journal-title":"Mol. 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