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首页> 外文期刊>Journal of mass spectrometry: JMS >Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience - Exemplified in amyotrophic lateral sclerosis biomarker discovery research
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Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience - Exemplified in amyotrophic lateral sclerosis biomarker discovery research

机译：基于高分辨率质谱的蛋白质组学在神经科学中的临床观点-以肌萎缩性侧索硬化生物标记物发现研究为例证

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摘要

Biomarker discovery is a central application in today's proteomic research. There is an urgent need for valid biomarkers to improve diagnostic tools and treatment in many disorders, such as the rapidly progressing neurodegenerative disorder amyotrophic lateral sclerosis (ALS) that has a fatal outcome in about 3 years and yet no curative treatment. Screening for clinically relevant biomarkers puts high demands on high-throughput, rapid and precise proteomic techniques. There is a large variety in the methods of choice involving mainly gel-based approaches as well as chromatographic techniques for multi-dimensional protein and peptide separations followed by mass spectrometry (MS) analysis. This special feature article will discuss some important aspects of MS-based clinical proteomics and biomarker discovery in the field of neuro degenerative diseases and ALS research respectively, with the aim to provide a prospective view on current and future research aspects in the field. Furthermore, examples for application of high-resolution MS-based proteomic strategies for ALS biomarker discovery will be demonstrated with two studies previously reported by our group. These studies include among others, utilization of capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) for advanced protein pattern classification in cerebrospinal fluid (CSF) samples of ALS patients as well as highly sensitive protein identification in minimal amounts of postmortem spinal cord tissue and laser micro-dissected motor neurons using FT-ICR-MS in conjunction with nanoflow LC coupled to matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (LC-MALDI-TOF-TOF-MS).
机译：生物标志物的发现是当今蛋白质组学研究的核心应用。迫切需要有效的生物标记物来改善许多疾病的诊断工具和治疗，例如快速发展的神经退行性疾病肌萎缩性侧索硬化症（ALS），其在约3年内可导致致命的后果，但尚无治疗方法。筛选临床相关的生物标志物对高通量，快速和精确的蛋白质组学技术提出了很高的要求。选择的方法种类繁多，主要包括基于凝胶的方法以及用于多维蛋白质和多肽分离，然后进行质谱（MS）分析的色谱技术。这篇专题文章将分别讨论神经退行性疾病和ALS研究领域基于MS的临床蛋白质组学和生物标记物发现的一些重要方面，以期对该领域的当前和未来研究方面提供前瞻性的见解。此外，我们小组先前报道的两项研究将证明基于高分辨率质谱的蛋白质组学策略在ALS生物标志物发现中的应用实例。这些研究包括利用毛细管液相色谱-傅立叶变换离子回旋共振质谱（LC-FTICR-MS）技术对ALS患者的脑脊液（CSF）样品进行高级蛋白质模式分类，以及极少地对高灵敏度蛋白质进行鉴定FT-ICR-MS与纳流液相色谱结合基质辅助激光解吸电离飞行时间串联质谱（LC-MALDI-TOF-TOF-MS）结合使用FT-ICR-MS分析大量的死后脊髓组织和激光显微切割的运动神经元）。

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