Clark D, Dedova I, Cordwell S, Matsumoto I
Department of Pathology, The University of Sydney, Sydney, NSW, Australia.
Mol Psychiatry. 2006 May;11(5):459-70, 423. doi: 10.1038/sj.mp.4001806.
The Anterior Cingulate Cortex (ACC, Brodmans Area 24) is implicated in the pathogenesis of schizophrenia due to its normal functions and connectivity together with reports of structural, morphological and neurotransmitter aberrations within this brain area in the disease state. Two-dimensional gel electrophoresis (2DE) was employed to scan and compare the ACC gray matter proteomes between schizophrenia (n = 10) and control (n = 10) post-mortem human tissue. This proteomic approach has detected 42 protein spots with altered levels in the schizophrenia cohort, which to our knowledge is the first proteomic analysis of the ACC in schizophrenia. Thirty nine of these proteins were subsequently identified using mass spectrometry and functionally classified into metabolism and oxidative stress, cytoskeletal, synaptic, signalling, trafficking and glial-specific groups. Some of the identified proteins have previously been implicated in the disease pathogenesis and some offer new insights into schizophrenia. Investigating these proteins, the genes encoding these proteins, their functions and interactions may shed light on the molecular mechanisms underlying the heterogeneous symptoms characteristic of schizophrenia.
前扣带回皮质(ACC,布罗德曼24区)由于其正常功能和连接性,以及在疾病状态下该脑区结构、形态和神经递质异常的报道,与精神分裂症的发病机制有关。采用二维凝胶电泳(2DE)扫描并比较精神分裂症患者(n = 10)和对照者(n = 10)死后人体组织中ACC灰质蛋白质组。这种蛋白质组学方法在精神分裂症队列中检测到42个蛋白点水平发生改变,据我们所知,这是首次对精神分裂症患者的ACC进行蛋白质组学分析。随后,其中39种蛋白质通过质谱鉴定,并在功能上分为代谢与氧化应激、细胞骨架、突触、信号传导、运输和神经胶质特异性组。一些已鉴定的蛋白质先前已被认为与疾病发病机制有关,还有一些为精神分裂症提供了新的见解。研究这些蛋白质、编码这些蛋白质的基因、它们的功能和相互作用,可能会揭示精神分裂症异质性症状背后的分子机制。