Cargando…
Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954794/ https://www.ncbi.nlm.nih.gov/pubmed/36831241 http://dx.doi.org/10.3390/cells12040574 |
_version_ | 1784894201205358592 |
---|---|
author | de Bartolomeis, Andrea Vellucci, Licia De Simone, Giuseppe Mazza, Benedetta Barone, Annarita Ciccarelli, Mariateresa |
author_facet | de Bartolomeis, Andrea Vellucci, Licia De Simone, Giuseppe Mazza, Benedetta Barone, Annarita Ciccarelli, Mariateresa |
author_sort | de Bartolomeis, Andrea |
collection | PubMed |
description | 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 50–80 nm at a distance of 20–40 nm creating “nanocolumns” 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’s 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. |
format | Online Article Text |
id | pubmed-9954794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99547942023-02-25 Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia de Bartolomeis, Andrea Vellucci, Licia De Simone, Giuseppe Mazza, Benedetta Barone, Annarita Ciccarelli, Mariateresa Cells Systematic Review 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 50–80 nm at a distance of 20–40 nm creating “nanocolumns” 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’s 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. MDPI 2023-02-10 /pmc/articles/PMC9954794/ /pubmed/36831241 http://dx.doi.org/10.3390/cells12040574 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Systematic Review de Bartolomeis, Andrea Vellucci, Licia De Simone, Giuseppe Mazza, Benedetta Barone, Annarita Ciccarelli, Mariateresa Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia |
title | Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia |
title_full | Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia |
title_fullStr | Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia |
title_full_unstemmed | Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia |
title_short | Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics’ Treatment of Schizophrenia |
title_sort | dysregulated signaling at postsynaptic density: a systematic review and translational appraisal for the pathophysiology, clinics, and antipsychotics’ treatment of schizophrenia |
topic | Systematic Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954794/ https://www.ncbi.nlm.nih.gov/pubmed/36831241 http://dx.doi.org/10.3390/cells12040574 |
work_keys_str_mv | AT debartolomeisandrea dysregulatedsignalingatpostsynapticdensityasystematicreviewandtranslationalappraisalforthepathophysiologyclinicsandantipsychoticstreatmentofschizophrenia AT velluccilicia dysregulatedsignalingatpostsynapticdensityasystematicreviewandtranslationalappraisalforthepathophysiologyclinicsandantipsychoticstreatmentofschizophrenia AT desimonegiuseppe dysregulatedsignalingatpostsynapticdensityasystematicreviewandtranslationalappraisalforthepathophysiologyclinicsandantipsychoticstreatmentofschizophrenia AT mazzabenedetta dysregulatedsignalingatpostsynapticdensityasystematicreviewandtranslationalappraisalforthepathophysiologyclinicsandantipsychoticstreatmentofschizophrenia AT baroneannarita dysregulatedsignalingatpostsynapticdensityasystematicreviewandtranslationalappraisalforthepathophysiologyclinicsandantipsychoticstreatmentofschizophrenia AT ciccarellimariateresa dysregulatedsignalingatpostsynapticdensityasystematicreviewandtranslationalappraisalforthepathophysiologyclinicsandantipsychoticstreatmentofschizophrenia |