Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia : Relevance of altered immune response
Vera-Montecinos, América (Institut de Recerca Sant Joan de Déu)
Rodríguez-Mias, Ricard (University of Washington. Department of Genome Sciences)
Vila, Èlia (Institut de Recerca Sant Joan de Déu)
Villén, Judit (University of Washington. Department of Genome Sciences)
Ramos, Belén (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2023
Resum:	The dorsolateral prefrontal cortex (DLPFC) has a crucial role in cognitive functioning and negative symptoms in schizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n = 20) and unaffected subjects (n = 20) followed by bioinformatic analysis to identify altered protein networks in schizophrenia (PXD024939 identifier in ProteomeXchange repository). Our results displayed a proteome profile in the DLPFC of 1989 proteins. 43 proteins were found significantly altered in schizophrenia. Analysis of this panel showed an enrichment of biological processes implicated in vesicle-mediated transport, processing and antigen presentation via MHC class II, intracellular transport and selenium metabolism. The enriched identified pathways were MHC class II antigen presentation, vesicle-mediated transport, Golgi ER retrograde transport, Nef mediated CD8 downregulation and the immune system. All these enriched categories were found to be downregulated. Furthermore, our network analyses showed crosstalk between proteins involved in MHC class II antigen presentation, membrane trafficking, Golgi-to-ER retrograde transport, Nef-mediated CD8 downregulation and the immune system with only one module built by 13 proteins. RAB7A showed eight interactions with proteins of all these pathways. Our results provide an altered molecular network involved in immune response in the DLPFC in schizophrenia with a central role of RAB7A. These results suggest that RAB7A or other proteins of this network could be potential targets for novel pharmacological strategies in schizophrenia for improving cognitive and negative symptoms.
Ajuts:	Instituto de Salud Carlos III MS16/00153 Instituto de Salud Carlos III CP16/00153 Instituto de Salud Carlos III CPII21/00008 Instituto de Salud Carlos III PI18/00213 Instituto de Salud Carlos III FI19/00080
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	DLPFC ; Schizophrenia ; Postmortem ; Molecular network ; Immune system
Publicat a:	Frontiers in Pharmacology, Vol. 14 (March 2023) , art. 1003557, ISSN 1663-9812

DOI: 10.3389/fphar.2023.1003557
PMID: 37033658

14 p, 2.3 MB

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