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The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment
BACKGROUND: For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (DISC1) is a gene implicated in the etiology of schizop...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
CMA Impact Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979657/ https://www.ncbi.nlm.nih.gov/pubmed/35361701 http://dx.doi.org/10.1503/jpn.210145 |
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author | Wang, Jijun Su, Ping Yang, Jian Xu, Lihua Yuan, Aihua Li, Chunbo Zhang, Tianhong Dong, Fang Zhou, Jingjing Samsom, James Wong, Albert H.C. Liu, Fang |
author_facet | Wang, Jijun Su, Ping Yang, Jian Xu, Lihua Yuan, Aihua Li, Chunbo Zhang, Tianhong Dong, Fang Zhou, Jingjing Samsom, James Wong, Albert H.C. Liu, Fang |
author_sort | Wang, Jijun |
collection | PubMed |
description | BACKGROUND: For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (DISC1) is a gene implicated in the etiology of schizophrenia, and we have found elevated levels of the D2R-DISC1 complex in the postmortem brain tissue of patients with schizophrenia. METHODS: We used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples. RESULTS: Levels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment. LIMITATIONS: Sample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands. CONCLUSION: Levels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia. |
format | Online Article Text |
id | pubmed-8979657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | CMA Impact Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89796572022-04-08 The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment Wang, Jijun Su, Ping Yang, Jian Xu, Lihua Yuan, Aihua Li, Chunbo Zhang, Tianhong Dong, Fang Zhou, Jingjing Samsom, James Wong, Albert H.C. Liu, Fang J Psychiatry Neurosci Research Paper BACKGROUND: For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (DISC1) is a gene implicated in the etiology of schizophrenia, and we have found elevated levels of the D2R-DISC1 complex in the postmortem brain tissue of patients with schizophrenia. METHODS: We used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples. RESULTS: Levels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment. LIMITATIONS: Sample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands. CONCLUSION: Levels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia. CMA Impact Inc. 2022-03-31 /pmc/articles/PMC8979657/ /pubmed/35361701 http://dx.doi.org/10.1503/jpn.210145 Text en © 2022 CMA Impact Inc. or its licensors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Research Paper Wang, Jijun Su, Ping Yang, Jian Xu, Lihua Yuan, Aihua Li, Chunbo Zhang, Tianhong Dong, Fang Zhou, Jingjing Samsom, James Wong, Albert H.C. Liu, Fang The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
title | The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
title_full | The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
title_fullStr | The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
title_full_unstemmed | The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
title_short | The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
title_sort | d2r-disc1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979657/ https://www.ncbi.nlm.nih.gov/pubmed/35361701 http://dx.doi.org/10.1503/jpn.210145 |
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