Faculty of Physics, West University of Timisoara, 4 Boulevard V. Parvan, Timisoara, Romania,
Adv Exp Med Biol. 2014;806:153-204. doi: 10.1007/978-3-319-06068-2_8.
Gangliosides, sialylated glycosphingolipids, are particularly enriched in mammalian central nervous system where their expression is cell type-specific and changes particularly during brain development, maturation, aging, and diseases. For this reason, gangliosides are important diagnostic markers for various brain ailments, including primary and secondary brain tumors and neurodegenerative diseases. Among all biochemical and biophysical methods employed so far for ganglioside analysis, mass spectrometry (MS) emerged as one of the most reliable due to the sensitivity, accuracy, and speed of analysis as well as the possibility to characterize in details the molecular structure of the identified biomarkers.This chapter presents significant achievements of MS with either electrospray (ESI), chip-based ESI, or matrix-assisted laser desorption/ionization (MALDI) in the analysis of gangliosides in normal and diseased human brain. Specifically, the chapter assesses the MS contribution in determination of topospecificity, filogenetic, and brain development stage dependence of ganglioside composition and structure as well as in discovery of ganglioside markers in neurodegenerative/neurodevelopmental conditions, primary and secondary brain tumors. The highlighted accomplishments in characterization of novel structures associated to severe brain pathologies show that MS has real perspectives to become a routine method for early diagnosis and therapy based on this biomolecule class.
神经节苷脂是唾液酸化的糖鞘脂，在哺乳动物中枢神经系统中含量特别丰富，其表达具有细胞类型特异性，并在大脑发育、成熟、衰老和疾病过程中发生显著变化。由于这个原因，神经节苷脂是各种脑疾病（包括原发性和继发性脑肿瘤和神经退行性疾病）的重要诊断标志物。在迄今为止用于神经节苷脂分析的所有生化和生物物理方法中，质谱（MS）因其分析的灵敏度、准确性和速度以及对鉴定生物标志物的分子结构进行详细表征的可能性而成为最可靠的方法之一。本章介绍了电喷雾（ESI）、基于芯片的 ESI 或基质辅助激光解吸/电离（MALDI）在正常和患病人脑神经节苷脂分析中的重要成果。具体而言，本章评估了 MS 在确定神经节苷脂组成和结构的拓扑特异性、系统发生和大脑发育阶段依赖性方面的贡献，以及在神经退行性/神经发育疾病、原发性和继发性脑肿瘤中发现神经节苷脂标志物方面的贡献。与严重脑病理相关的新型结构的特征化方面的突出成就表明，MS 具有成为基于此类生物分子的早期诊断和治疗常规方法的实际前景。
