Abstract
Gangliosides are effective biochemical markers of brain pathologies, being also in the focus of research as potential therapeutic targets. Accurate brain ganglioside mapping is an essential requirement for correlating the specificity of their composition with a certain pathological state and establishing a well-defined set of biomarkers. Among all bioanalytical methods conceived for this purpose, mass spectrometry (MS) has developed into one of the most valuable, due to the wealth and consistency of structural information provided. In this context, the present article reviews the achievements of MS in discovery and structural analysis of gangliosides associated with severe brain pathologies. The first part is dedicated to the contributions of MS in the assessment of ganglioside composition and role in the specific neurodegenerative disorders: Alzheimer’s and Parkinson’s diseases. A large subsequent section is devoted to cephalic disorders (CD), with an emphasis on the MS of gangliosides in anencephaly, the most common and severe disease in the CD spectrum. The last part is focused on the major accomplishments of MS-based methods in the discovery of ganglioside species, which are associated with primary and secondary brain tumors and may either facilitate an early diagnosis or represent target molecules for immunotherapy oriented against brain cancers.
Highlights
Gangliosides (GGs) represent a particular class of glycosphingolipids with a complex structure, ubiquitously identified in tissues and body fluids, and highly expressed in the central nervous system (CNS), in particular in various brain regions [1,2,3]
If this study provided mainly quantitative data, the extended mass spectrometry (MS) investigation carried out in 2008 by employing fully automated chip nanoESI high capacity ion trap (HCT) MS and multistage MS (MSn) by collision-induced dissociation (CID) provided important information related to the GG expression in anencephalic vs. age-matched normal brain tissue [139,140]
To achieve novel insights into their functional characteristics, understand the many biological events in which these molecules are implicated, and exploit them as markers of brain diseases or therapeutic agents, the scientists in the field rely on the advancements in bioanalytics and biotechnology
Summary
Gangliosides (GGs) represent a particular class of glycosphingolipids with a complex structure, ubiquitously identified in tissues and body fluids, and highly expressed in the central nervous system (CNS), in particular in various brain regions [1,2,3]. Extended into the extracellular environment, the glycan core, especially through the terminal sialic acid residues [6], participates in specific and essential biological functions of the brain [3], such as cell-to-cell recognition/communication and signaling, modulating, or triggering a variety of biological events, including those related to brain development, maturation, and aging [7,8,9,10]. At the nervous system level, the expression, distribution, and structure of GGs are cell and tissue type-specific and vary during tissue development, maturation, aging, and most. At the nervous system level, the expression, distribution, and structure of GGs are cell and tissue type‐specific and vary during tissue development, maturation, aging, and omf aolls,tionfpaallt,hinolpoagtihcaollosgtaicteasl s[t1a2t,e1s3][.12A,1n3i]n. While for many conditions, including cancer [32], diabetes [33], and infection [34], the key role of GGs is recognized and effective treatments have been identified, for many degenerative neurological diseases no reported progress has so far been reported in this direction [35]
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