engleski

Human Brain Gangliosides in Health and Disease: Fingerprinting by Modern Mass Spectrometry

Gangliosides, a large group of sialylated glycosphingolipids, are building components of plasma-membrane and glycocalyx of eukaryotic cells, participating in functions of membrane microdomains (lipid rafts) and defining antigenic composition of cell surfaces. As such, they participate in cell-to-cell recognition/communication and cell signaling. Brain cells, particularly neurons, contain gangliosides in much higher concentrations than any other cell type. Ganglioside composition is species- and cell type-specific and specifically changes during brain development, maturation, aging and diseases, such as neurodegeneration, malignant alteration etc. Therefore, gangliosides could be used as valuable tissue-stage markers and/or diagnostic markers of diseases, and serve as therapeutic targets as well as therapeutic agents. In order to achieve reliable, systematic, detailed and comparative composition/structure characterization of gangliosides isolated as complex mixtures from brain tissue samples we have developed and optimized fast and sensitive mass spectrometric approaches allowing ganglioside screening and sequencing directly from the mixture [1, 2]. Here, we report results of the composition and structure analysis of native ganglioside mixtures from selected regions of human fetal and adult brain, brain tumors (gliosarcoma, meningeoma, hemangioma etc.), and cerebral remnant in anencephaly (a congenital brain malformation). The results were obtained employing capillary- or fully automated chip-based nanoelectrospray ionization interfaced to high-performance tandem mass spectrometers: a high capacity ion trap MS, quadrupole time-of-flight MS, and Fourier transform ion cyclotron resonance MS. The MS approaches complemented with thin-layer chromatographic and immunochemical methods enabled detection and structural assignment of more than 100 individual ganglioside species including minor species. In conclusion, the MS strategies for screening and structural analysis of gangliosides provide a significant impact to the understanding of functional and pathologic implications of gangliosides in the nervous system and are powerful tool for defining diagnostically useful biomarkers.

gangliosides; human brain; biomarkers; mass spectrometry

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