Huzarewich Rhiannon L C H, Siemens Christine G, Booth Stephanie A
Molecular PathoBiology, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada R3E3R2.
J Biomed Biotechnol. 2010;2010:613504. doi: 10.1155/2010/613504. Epub 2010 Mar 4.
The advent of genomics and proteomics has been a catalyst for the discovery of biomarkers able to discriminate biological processes such as the pathogenesis of complex diseases. Prompt detection of prion diseases is particularly desirable given their transmissibility, which is responsible for a number of human health risks stemming from exogenous sources of prion protein. Diagnosis relies on the ability to detect the biomarker PrP(Sc), a pathological isoform of the host protein PrP(C), which is an essential component of the infectious prion. Immunochemical detection of PrP(Sc) is specific and sensitive enough for antemortem testing of brain tissue, however, this is not the case in accessible biological fluids or for the detection of recently identified novel prions with unique biochemical properties. A complementary approach to the detection of PrP(Sc) itself is to identify alternative, "surrogate" gene or protein biomarkers indicative of disease. Biomarkers are also useful to track the progress of disease, especially important in the assessment of therapies, or to identify individuals "at risk". In this review we provide perspective on current progress and pitfalls in the use of "omics" technologies to screen body fluids and tissues for biomarker discovery in prion diseases.
基因组学和蛋白质组学的出现推动了生物标志物的发现,这些生物标志物能够区分复杂疾病发病机制等生物学过程。鉴于朊病毒疾病具有传染性,会带来许多源于外源朊病毒蛋白的人类健康风险,因此对其进行快速检测尤为重要。诊断依赖于检测生物标志物PrP(Sc)的能力,PrP(Sc)是宿主蛋白PrP(C)的病理性异构体,是传染性朊病毒的重要组成部分。PrP(Sc)的免疫化学检测对于脑组织的生前检测具有足够的特异性和敏感性,然而,在可获取的生物体液中或检测最近发现的具有独特生化特性的新型朊病毒时并非如此。检测PrP(Sc)本身的一种补充方法是识别指示疾病的替代“替代”基因或蛋白质生物标志物。生物标志物也有助于追踪疾病进展,这在评估治疗方法时尤为重要,或者用于识别“有风险”的个体。在这篇综述中,我们阐述了利用“组学”技术筛查体液和组织以发现朊病毒疾病生物标志物的当前进展和陷阱。