Vera-Montecinos América, Rodríguez-Mias Ricard, Vila Èlia, Villén Judit, Ramos Belén
Psiquiatria Molecular, Parc Sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Sant Boi de Llobregat, Spain.
Department of Genome Sciences, School of Medicine, University of Washington, Seattle, WA, United States.
Front Pharmacol. 2023 Mar 23;14:1003557. doi: 10.3389/fphar.2023.1003557. eCollection 2023.
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 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.
背外侧前额叶皮层（DLPFC）在精神分裂症的认知功能和阴性症状中起着关键作用。然而，关于该区域在精神分裂症中蛋白质网络改变的信息有限。我们对慢性精神分裂症患者（n = 20）和未受影响的受试者（n = 20）死后DLPFC灰质进行了单次液相色谱 - 串联质谱蛋白质组学分析，随后进行生物信息学分析以识别精神分裂症中改变的蛋白质网络（蛋白质组交换库中的标识符PXD024939）。我们的结果显示DLPFC中有1989种蛋白质的蛋白质组图谱。发现43种蛋白质在精神分裂症中显著改变。对该组的分析表明，与囊泡介导的运输、加工和抗原呈递MHC II类、细胞内运输和硒代谢相关的生物过程富集。富集的确定途径是MHC II类抗原呈递、囊泡介导的运输、高尔基体 - 内质网逆行运输、Nef介导的CD8下调和免疫系统。所有这些富集类别均被发现下调。此外，我们的网络分析显示，参与MHC II类抗原呈递、膜运输、高尔基体到内质网逆行运输、Nef介导的CD8下调和免疫系统的蛋白质之间存在串扰，只有一个由13种蛋白质组成的模块。RAB7A与所有这些途径的蛋白质有8种相互作用。我们的结果提供了一个在精神分裂症DLPFC中参与免疫反应的改变的分子网络，其中RAB7A起核心作用。这些结果表明，RAB7A或该网络中的其他蛋白质可能是精神分裂症新型药物策略改善认知和阴性症状的潜在靶点。
