Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress
Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress
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DOI：
10.1038/sj.mp.4001511
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发表时间：
2004-07-01
影响因子：
11
通讯作者：
Bahn, S
中科院分区：
文献类型：
--
作者：
Prabakaran, S;Swatton, JE;Bahn, S
精神分裂症的病因和病理生理学仍不清楚。采用转录组学、蛋白质组学和代谢组学的并行方法对人脑组织进行分子疾病特征的研究。通过蛋白质组学鉴定，几乎一半的改变蛋白与线粒体功能和氧化应激反应有关。这反映在转录和代谢物的扰动上。转录改变的聚类分析显示，与能量代谢和氧化应激相关的基因将近90%的精神分裂症患者与对照组区分开来，同时可以排除混淆药物效应的可能性。我们认为氧化应激和随之而来的细胞适应与精神分裂症的疾病过程有关，并希望这一新的疾病概念可以促进精神分裂症和相关综合征的治疗、诊断和疾病预防。
The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.