MS-based glycomics: An analytical tool to assess nervous system diseases

Abstract

Neurological diseases affect millions of peopleochemistryorldwide and are continuously increasing due to the globe’s aging population. Such diseases affect the nervous system and are characterized by a progressive decline in brain function and progressive cognitive impairment, decreasing the quality of life for those with the disease as well as for their families and loved ones. The increased burden of nervous system diseases demands a deeper insight into the biomolecular mechanisms at work during disease development in order to improve clinical diagnosis and drug design. Recently, evidence has related glycosylation to nervous system diseases. Glycosylation is a vital post-translational modification that mediates many biological functions, and aberrant glycosylation has been associated with a variety of diseases. Thus, the investigation of glycosylation in neurological diseases could provide novel biomarkers and information for disease pathology. During the last decades, many techniques have been developed for facilitation of reliable and efficient glycomic analysis. Among these, mass spectrometry (MS) is considered the most powerful tool for glycan analysis due to its high resolution, high sensitivity, and the ability to acquire adequate structural information for glycan identification. Along with MS, a variety of approaches and strategies are employed to enhance the MS-based identification and quantitation of glycans in neurological samples. Here, we review the advanced glycomic tools used in nervous system disease studies, including separation techniques prior to MS, fragmentation techniques in MS, and corresponding strategies. The glycan markers in common clinical nervous system diseases discovered by utilizing such MS-based glycomic tools are also summarized and discussed.

Severe kidney dysfunction in sialidosis mice reveals an essential role for neuraminidase 1 in reabsorption

“…Table 1 and Supplemental Table 4 list all the sialylated glycoforms accumulated in Neu1 ΔEx3 kidney tissues and provide a relative quantitative comparison between WT and Neu1 ΔEx3 mice. To analyze sialic acid linkages, we also performed N-glycoprofiling by HILIC-UPLC-FLR-ESI-MS ( 37 ) capable of distinguishing between α2,3- and α2,6-linked sialic acids ( 38 ). These analyses verified major increases of oligomannose and sialylated N-glycans in Neu1 ΔEx3 mice ( Supplemental Figure 8A ) and indicated that the ratio of α2,3- to α2,6-linked sialic acids was similar in WT and in Neu1 ΔEx3 mice, as illustrated by the representative extracted ion current for the disialo-biantennary core-fucosylated structure with m/z 1,341.0150 ( Supplemental Figure 8B ).…”

Alzheimer’s disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice

“…It is interesting to speculate the potential role trans ligands of CD33M could have in vivo. This is especially worth exploring in the context of AD brain, as dramatic changes have been observed in the brain glycome of animal models of AD as well as human patients [69][70][71]. Recent advances in understanding human sialome and elucidation of the glycan ligands of CD33 [72][73][74][75] could be instrumental in spatial characterization of glycan ligands of CD33M at both regional and cellular levels in the brain, their changes during the course of disease, and their potential role in modulating microglia.…”

The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms

“…Although the site of modification was not established, these two glycosylated proteoforms were significantly increased in the patients with MuSc with respect to healthy controls. Indeed, altered glycoprotein expression and glycosylation aberrations, consisting of increased glycan size, extra branching of glycan chains, over-sialylation, or over-fucosylation, were associated with many diseases, especially cancer and neurological disorders [ 165 , 166 ]. A recent magistral review [ 158 ] evidences the complexity of the relationships between enzymatic glycosylation and other factors and their molecular alterations as potential diagnostic markers in many diseases.…”