Schizophrenia as a disorder of molecular pathways.

Schizophrenia as a disorder of molecular pathways.
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DOI:
10.1016/j.biopsych.2014.01.001
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发表时间:
2015-01-01
影响因子:
10.6
通讯作者:
Mirnics, Karoly
Mirnics, Karoly
中科院分区:
医学1区
文献类型:
--
作者:
Horvath, Szatmar;Mirnics, Karoly

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在过去的十年中,对精神分裂症患者死后组织的转录组研究表明,突触、线粒体、免疫系统、GABA 能和少突胶质细胞的变化都是疾病过程中不可或缺的部分。遗传和转录组学的综合研究表明,该疾病的分子基础甚至比精神分裂症的症状多样性还要多样化。最终,为了破译人类疾病的病理生理学,我们需要了解基因组中数百个基因和调控元件的功能,以及它们在发育背景下过度表达和表达减少的后果。此外,来自各种数据源的知识的整合仍然是一个巨大的挑战,必须在未来几十年内系统地解决。最终,我们能否成功地解释精神分裂症的分子变化将取决于我们利用创新思想理解生物学的能力,而不是依赖于开发新颖、更强大的技术的希望。
Over the last decade transcriptome studies of postmortem tissue from subjects with schizophrenia revealed that synaptic, mitochondrial, immune system, GABA-ergic and oligodendrocytic changes are all integral parts of the disease process. The combined genetic and transcriptomics studies argue that the molecular underpinnings of the disease are even more varied than the symptomatic diversity of schizophrenia. Ultimately, to decipher the pathophysiology of human disorders in general, we will need to understand the function of hundreds of genes and regulatory elements in our genome, and the consequences of their overexpression and reduced expression in a developmental context. Furthermore, integration of knowledge from various data sources remains a monumental challenge that has to be systematically addressed in the upcoming decades. In the end, our success in interpreting the molecular changes in schizophrenia will depend on our ability to understand the biology using innovative ideas and cannot depend on the hope of developing novel, more powerful technologies.
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