Table3_Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia: Relevance of altered immune response.XLSX

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.

背外侧前额叶皮层（DLPFC）在认知功能和精神分裂症的阴性症状中扮演着至关重要的角色。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。本研究采用单次液相色谱-串联质谱法对慢性精神分裂症患者（n = 20）和无症状受试者（n = 20）的尸检DLPFC灰质进行了蛋白质组学分析，随后进行生物信息学分析，以识别精神分裂症中的蛋白质网络改变（ProteomeXchange库中的PXD024939标识符）。我们的结果显示，DLPFC中共有1989种蛋白质的蛋白质组特征。在精神分裂症患者中发现了43种蛋白质显著改变。对这些蛋白质组的研究揭示了涉及囊泡介导的运输、处理和通过MHC II类途径的抗原呈递的生物过程的富集，包括细胞内运输和硒代谢。富集的识别通路包括MHC II类抗原呈递、囊泡介导的运输、高尔基体-内质网逆向运输、Nef介导的CD8下调以及免疫系统。所有这些富集的类别均被发现下调。此外，我们的网络分析显示，MHC II类抗原呈递、膜运输、高尔基体到内质网的逆向运输、Nef介导的CD8下调和免疫系统中的蛋白质之间存在交互作用，仅由13个蛋白质构建的一个模块。RAB7A与这些通路中的所有蛋白质进行了八个相互作用。我们的结果提供了精神分裂症DLPFC中参与免疫反应的蛋白质网络的改变情况，其中RAB7A起着核心作用。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理学策略中改善认知和阴性症状的潜在靶点。