Gangliosides as Biomarkers of Human Brain Diseases: Trends in Discovery and Characterization by High-Performance Mass Spectrometry

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.

Gangliosidome of a Human Hippocampus in Temporal Lobe Epilepsy Resolved by High-Resolution Tandem Mass Spectrometry

“…For gangliosides assignment, the abbreviation system introduced by Svennerholm [42], together with the recommendations of IUPAC-IUB Commission on Biochemical Nomenclature (IUPAC-IUB 1998) were used. The ion assignment was based on exact mass calculation and the knowledge we have acquired in our previous studies [10,19,21,22,25] on this type of molecules and the biosynthesis pathways of gangliosides. The assignment of the fragment ions generated within the HCD MS/MS fragmentation experiments followed the nomenclature introduced by Domon and Costello [43] and revised by Costello et al [44].…”

“…The diversity of ganglioside structures provides huge variability of their interactions with other membrane lipids and proteins, influencing membrane dynamics and homeostasis. Thus, the utilization of highly sensitive modern mass spectrometric methods has so far enabled detailed structural characterization of human brain gangliosides, and revealed the presence of novel or modified ganglioside structures viewed as specific pathological, diagnostic markers or potential therapeutic targets [10,11]. Alterations in brain ganglioside composition or metabolism have been found in different neurological and neuropsychiatric conditions and are considered to be involved in complex molecular pathogenesis of neurodegeneration [12][13][14][15].…”

Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine

“…Gangliosides with complex carbohydrate head groups, are most abundantly found in the CNS and are involved in several functions such as cell–cell recognition, signal transduction, synaptic transmission, cognition and oligodendrocyte differentiation [ 162 , 163 ]. The composition of gangliosides within the CNS changes during neurodevelopment: from simplest gangliosides GD3 and GM3 expressed primarily in early development stages, to more complex gangliosides such as GM1, GD1a and GD1b dominate in later stages and adult brains [ 164 , 165 ].…”

Can Serum IgG Antiganglioside Antibodies to GM1, GM3 and GD1a be Used as Markers in Patients with Ischemic Stroke?

“…The expression patterns of gangliosides vary in different tissues, during different life periods, as well as in various pathologies [1,9,11,12]. The antiganglioside antibodies (AGAs) have the potential to be suitable diagnostic and therapeutic biomarkers for many brain abnormalities [14]. The ganglioside composition is related with a certain disorder [14].…”

“…The antiganglioside antibodies (AGAs) have the potential to be suitable diagnostic and therapeutic biomarkers for many brain abnormalities [14]. The ganglioside composition is related with a certain disorder [14]. Our team has been working with multiple sclerosis (MS), Alzheimer's disease (AD) and aging people for many years [7,8,16].…”