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精神分裂症蛋白质组学:迈向检验医学的生物标志物?

Schizophrenia proteomics: biomarkers on the path to laboratory medicine?

作者信息

Lakhan Shaheen Emmanuel

机构信息

Global Neuroscience Initiative Foundation, Los Angeles, CA, USA.

出版信息

Diagn Pathol. 2006 Jul 17;1:11. doi: 10.1186/1746-1596-1-11.

Abstract

Over two million Americans are afflicted with schizophrenia, a debilitating mental health disorder with a unique symptomatic and epidemiological profile. Genomics studies have hinted towards candidate schizophrenia susceptibility chromosomal loci and genes. Modern proteomic tools, particularly mass spectrometry and expression scanning, aim to identify both pathogenic-revealing and diagnostically significant biomarkers. Only a few studies on basic proteomics have been conducted for psychiatric disorders relative to the plethora of cancer specific experiments. One such proteomic utility enables the discovery of proteins and biological marker fingerprinting profiling techniques (SELDI-TOF-MS), and then subjects them to tandem mass spectrometric fragmentation and de novo protein sequencing (MALDI-TOF/TOF-MS) for the accurate identification and characterization of the proteins. Such utilities can explain the pathogenesis of neuro-psychiatric disease, provide more objective testing methods, and further demonstrate a biological basis to mental illness. Although clinical proteomics in schizophrenia have yet to reveal a biomarker with diagnostic specificity, methods that better characterize the disorder using endophenotypes can advance findings. Schizophrenia biomarkers could potentially revolutionize its psychopharmacology, changing it into a more hypothesis and genomic/proteomic-driven science.

摘要

超过两百万美国人患有精神分裂症,这是一种使人衰弱的心理健康障碍,具有独特的症状和流行病学特征。基因组学研究已经暗示了精神分裂症候选易感染色体位点和基因。现代蛋白质组学工具,尤其是质谱分析和表达扫描,旨在识别揭示致病机制和具有诊断意义的生物标志物。相对于大量针对癌症的特定实验,关于精神疾病的基础蛋白质组学研究仅有少数几项。一种这样的蛋白质组学应用能够发现蛋白质和生物标志物指纹图谱分析技术(表面增强激光解吸电离飞行时间质谱),然后对其进行串联质谱裂解和从头蛋白质测序(基质辅助激光解吸电离飞行时间串联质谱),以准确鉴定和表征蛋白质。这样的应用能够解释神经精神疾病的发病机制,提供更客观的检测方法,并进一步证明精神疾病的生物学基础。尽管精神分裂症的临床蛋白质组学尚未发现具有诊断特异性的生物标志物,但使用内表型更好地表征该疾病的方法可以推动研究进展。精神分裂症生物标志物可能会彻底改变其精神药理学,使其转变为一门更受假设和基因组学/蛋白质组学驱动的科学。

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