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Psychiatric disorders biochemical pathways unraveled by human brain proteomics

机译:精神疾病:人脑蛋白质组学揭示的生化途径

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Approximately 25 of the world population is affected by a mental disorder at some point in their life. Yet, only in the mid-twentieth century a biological cause has been proposed for these diseases. Since then, several studies have been conducted toward a better comprehension of those disorders, and although a strong genetic influence was revealed, the role of these genes in disease mechanism is still unclear. This led most recent studies to focus on the molecular basis of mental disorders. One line of investigation that has risen in the post-genomic era is proteomics, due to its power of revealing proteins and biochemical pathways associated with biological systems. Therefore, this review compiled and analyzed data of differentially expressed proteins, which were found in postmortem brain studies of the three most prevalent psychiatric diseases: schizophrenia, bipolar disorder and major depressive disorders. Overviewing both the proteomic methods used in postmortem brain studies, the most consistent metabolic pathways found altered in these diseases. We have unraveled those disorders share about 21 of proteins affected, and though most are related to energy metabolism pathways deregulation, the main differences found are 14-3-3-mediated signaling in schizophrenia, mitochondrial dysfunction in bipolar disorder and oxidative phosphorylation in depression.
机译:世界上大约25%的人口在他们生命中的某个阶段受到精神障碍的影响。然而,直到二十世纪中叶,才提出了这些疾病的生物学原因。从那时起,已经进行了几项研究,以更好地理解这些疾病,尽管揭示了强烈的遗传影响,但这些基因在疾病机制中的作用仍不清楚。这导致最近的研究集中在精神障碍的分子基础上。在后基因组时代兴起的一条研究线是蛋白质组学,因为它能够揭示与生物系统相关的蛋白质和生化途径。因此,本综述汇编并分析了差异表达蛋白的数据,这些数据是在三种最普遍的精神疾病(精神分裂症、双相情感障碍和重度抑郁症)的死后脑部研究中发现的。概述死后脑研究中使用的蛋白质组学方法,在这些疾病中发现的最一致的代谢途径发生了变化。我们已经解开了这些疾病共享约21%的受影响蛋白质,尽管大多数与能量代谢途径失调有关,但发现的主要差异是精神分裂症中的14-3-3介导信号,双相情感障碍中的线粒体功能障碍和抑郁症中的氧化磷酸化。

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