Martins-de-Souza Daniel, Gattaz Wagner F, Schmitt Andrea, Maccarrone Giuseppina, Hunyadi-Gulyás Eva, Eberlin Marcos N, Souza Gustavo H M F, Marangoni Sérgio, Novello José C, Turck Christoph W, Dias-Neto Emmanuel
Laboratório de Neurociências, Instituto de Psiquiatria, Faculdade de Medicina da USP, Rua Dr. Ovídio Pires de Campos, SP, Brazil.
J Psychiatr Res. 2009 Jul;43(11):978-86. doi: 10.1016/j.jpsychires.2008.11.006. Epub 2008 Dec 24.
Schizophrenia is likely to be a consequence of serial alterations in a number of genes that, together with environmental factors, will lead to the establishment of the illness. The dorsolateral prefrontal cortex (Brodmann's Area 46) is implicated in schizophrenia and executes high functions such as working memory, differentiation of conflicting thoughts, determination of right and wrong concepts, correct social behavior and personality expression. We performed a comparative proteome analysis using two-dimensional gel electrophoresis of pools from 9 schizophrenia and 7 healthy control patients' dorsolateral prefrontal cortex aiming to identify, by mass spectrometry, alterations in protein expression that could be related to the disease. In schizophrenia-derived samples, our analysis revealed 10 downregulated and 14 upregulated proteins. These included alterations previously implicated in schizophrenia, such as oligodendrocyte-related proteins (myelin basic protein and transferrin), as well as malate dehydrogenase, aconitase, ATP synthase subunits and cytoskeleton-related proteins. Also, six new putative disease markers were identified, including energy metabolism, cytoskeleton and cell signaling proteins. Our data not only reinforces the involvement of proteins previously implicated in schizophrenia, but also suggests new markers, providing further information to foster the comprehension of this important disease.
精神分裂症可能是多种基因发生一系列改变的结果，这些基因与环境因素共同作用，会导致该疾病的发生。背外侧前额叶皮质（布罗德曼46区）与精神分裂症有关，执行诸如工作记忆、区分相互冲突的想法、确定是非观念、正确的社会行为和个性表达等高级功能。我们使用来自9名精神分裂症患者和7名健康对照者的背外侧前额叶皮质样本进行二维凝胶电泳，进行了比较蛋白质组分析，旨在通过质谱鉴定可能与该疾病相关的蛋白质表达变化。在精神分裂症患者的样本中，我们的分析发现了10种下调蛋白和14种上调蛋白。这些包括先前与精神分裂症有关的改变，如少突胶质细胞相关蛋白（髓鞘碱性蛋白和转铁蛋白），以及苹果酸脱氢酶、乌头酸酶、ATP合酶亚基和细胞骨架相关蛋白。此外，还鉴定出6种新的潜在疾病标志物，包括能量代谢、细胞骨架和细胞信号蛋白。我们的数据不仅强化了先前与精神分裂症有关的蛋白质的参与，还提出了新的标志物，为增进对这一重要疾病的理解提供了更多信息。
