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精神分裂症死后大脑白质和灰质的核蛋白质组

The Nuclear Proteome of White and Gray Matter from Schizophrenia Postmortem Brains.

作者信息

Saia-Cereda Verônica M, Santana Aline G, Schmitt Andrea, Falkai Peter, Martins-de-Souza Daniel

机构信息

Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.

Department of Psychiatry and Psychotherapy, Ludwig Maximilian University (LMU), Munich, Germany.

出版信息

Mol Neuropsychiatry. 2017 Jul;3(1):37-52. doi: 10.1159/000477299. Epub 2017 Jun 17.

Abstract

Schizophrenia (SCZ) is a serious neuropsychiatric disorder that manifests through several symptoms from early adulthood. Numerous studies over the last decades have led to significant advances in increasing our understanding of the factors involved in SCZ. For example, mass spectrometry-based proteomic analysis has provided important insights by uncovering protein dysfunctions inherent to SCZ. Here, we present a comprehensive analysis of the nuclear proteome of postmortem brain tissues from corpus callosum (CC) and anterior temporal lobe (ATL). We show an overview of the role of deregulated nuclear proteins in these two main regions of the brain: the first, mostly composed of glial cells and axons of neurons, and the second, represented mainly by neuronal cell bodies. These samples were collected from SCZ patients in an attempt to characterize the role of the nucleus in the disease process. With the ATL nucleus enrichment, we found 224 proteins present at different levels, and 76 of these were nuclear proteins. In the CC analysis, we identified 119 present at different levels, and 24 of these were nuclear proteins. The differentially expressed nuclear proteins of ATL are mainly associated with the spliceosome, whereas those of the CC region are associated with calcium/calmodulin signaling.

摘要

精神分裂症(SCZ)是一种严重的神经精神障碍,从成年早期开始就会表现出多种症状。在过去几十年里,众多研究在增进我们对精神分裂症相关因素的理解方面取得了重大进展。例如,基于质谱的蛋白质组学分析通过揭示精神分裂症固有的蛋白质功能障碍提供了重要见解。在此,我们对胼胝体(CC)和颞叶前部(ATL)的死后脑组织细胞核蛋白质组进行了全面分析。我们展示了大脑这两个主要区域中失调的核蛋白的作用概述:第一个区域主要由神经胶质细胞和神经元轴突组成,第二个区域主要由神经元细胞体代表。这些样本取自精神分裂症患者,旨在确定细胞核在疾病过程中的作用。通过ATL细胞核富集,我们发现224种蛋白质存在不同程度的表达,其中76种为核蛋白。在CC分析中,我们鉴定出119种存在不同程度表达的蛋白质,其中24种为核蛋白。ATL中差异表达的核蛋白主要与剪接体相关,而CC区域的核蛋白则与钙/钙调蛋白信号传导相关。

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