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[蛋白质组学:精神病学中的生物标志物研究]

[Proteomics: biomarker research in psychiatry].

作者信息

Hünnerkopf R, Grassl J, Thome J

机构信息

Department of Psychiatry, The School of Medicine, University of Wales Swansea, UK.

出版信息

Fortschr Neurol Psychiatr. 2007 Oct;75(10):579-86. doi: 10.1055/s-2007-959249. Epub 2007 Jun 13.

Abstract

Over the last decade, genomics research in psychiatry and neuroscience has provided important insights into genes expressed under different physiological and pathophysiological conditions. Contrary to the great expectations regarding a clinical use of these datasets, genomics failed to improve markedly the diagnostic and therapeutic options in brain disorders. Due to alternative splicing and posttranslational modifications, one single gene determines a multitude of gene products. Therefore, in order to understand molecular processes in neuropsychiatric disorders, it is necessary to unravel signal transduction pathways and complex interaction networks on the level of proteins, not only DNA and mRNA. Proteomics utilises high-throughput mass spectrometric protein identification that can reveal protein expression levels, posttranslational modifications and protein-protein interactions. Proteomic tools have the power to identify quantitative and qualitative protein patterns in postmortem brain tissue, cerebrospinal fluid (CSF) or serum, thus increasing the knowledge about etiology and pathomechanisms of brain diseases. Comparing protein profiles in healthy and disease states provides an opportunity to establish specific diagnostic and prognostic biomarkers. In addition, proteomic studies of the effects of medication - in vitro and in vivo - might help to design specific pharmaceutical agents with fewer side effects. In this overview, we present the most widely used proteomic techniques and illustrate the potential and limitations of this field of research. Furthermore, we provide insight into the contributions of proteomics to the study of psychiatric diseases such as Alzheimer's disease, drug addiction, schizophrenia and depression.

摘要

在过去十年中,精神病学和神经科学领域的基因组学研究为不同生理和病理生理条件下表达的基因提供了重要见解。与对这些数据集临床应用的巨大期望相反,基因组学未能显著改善脑部疾病的诊断和治疗选择。由于可变剪接和翻译后修饰,单个基因可决定多种基因产物。因此,为了理解神经精神疾病中的分子过程,不仅有必要在DNA和mRNA层面,还需在蛋白质层面揭示信号转导途径和复杂的相互作用网络。蛋白质组学利用高通量质谱蛋白质鉴定技术,可揭示蛋白质表达水平、翻译后修饰以及蛋白质 - 蛋白质相互作用。蛋白质组学工具能够识别死后脑组织、脑脊液(CSF)或血清中的定量和定性蛋白质模式,从而增加对脑部疾病病因和发病机制的了解。比较健康状态和疾病状态下的蛋白质谱,为建立特定的诊断和预后生物标志物提供了机会。此外,对药物在体外和体内作用的蛋白质组学研究,可能有助于设计副作用更少的特定药物制剂。在本综述中,我们介绍了最广泛使用的蛋白质组学技术,并阐述了该研究领域的潜力和局限性。此外,我们还深入探讨了蛋白质组学对诸如阿尔茨海默病、药物成瘾、精神分裂症和抑郁症等精神疾病研究的贡献。

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