Neurological analyses: Focus on gangliosides and mass spectrometry

Abstract

Gangliosides, sialylated glycosphingolipids, are particularly enriched in mammalian central nervous system where their expression is cell type-specifi c 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 identifi ed biomarkers. This chapter presents signifi cant 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. Specifi cally, the chapter assesses the MS contribution in determination of topospecifi city, fi logenetic, 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.