Mass Spectrometry Imaging for Glycome in the Brain

Abstract

Glycans are diverse structured biomolecules that play crucial roles in various biological processes. Glycosylation, an enzymatic system through which various glycans are bound to proteins and lipids, is the most common and functionally crucial post-translational modification process. It is known to be associated with brain development, signal transduction, molecular trafficking, neurodegenerative disorders, psychopathologies, and brain cancers. Glycans in glycoproteins and glycolipids expressed in brain cells are involved in neuronal development, biological processes, and central nervous system maintenance. The composition and expression of glycans are known to change during those physiological processes. Therefore, imaging of glycans and the glycoconjugates in the brain regions has become a “hot” topic nowadays. Imaging techniques using lectins, antibodies, and chemical reporters are traditionally used for glycan detection. However, those techniques offer limited glycome detection. Mass spectrometry imaging (MSI) is an evolving field that combines mass spectrometry with histology allowing spatial and label-free visualization of molecules in the brain. In the last decades, several studies have employed MSI for glycome imaging in brain tissues. The current state of MSI uses on-tissue enzymatic digestion or chemical reaction to facilitate successful glycome imaging. Here, we reviewed the available literature that applied MSI techniques for glycome visualization and characterization in the brain. We also described the general methodologies for glycome MSI and discussed its potential use in the three-dimensional MSI in the brain.

Distinct patterns of plaque and microglia glycosylation in Alzheimer's disease

“…N ‐glycoproteomic analysis of human AD brains found dysregulated N ‐glycosylation associated with extracellular matrix dysfunction, neuroinflammation, synaptic dysfunction, cell adhesion alteration, lysosomal dysfunction, endocytic trafficking dysregulation, endoplasmic reticulum dysfunction, and cell signaling dysregulation [ 20 ]. Recent advances in brain matrix‐assisted lasor desorption/ionization mass spectrometry imaging (MALDI‐MSI) offer the promise of regional and subcellular resolution [ 49 ] that will further advance our understanding of the spatial organization of the glycome in AD. Early MSI studies in the AD dentate gyrus found disordered localization of the glycolipid ganglioside GM1 [ 50 ], while a recent study found hyper N ‐glycosylation within the frontal cortex in the 5XFAD mouse model of amyloid pathology and rTg4510 mouse model of tau pathology.…”

Changes in tissue protein N-glycosylation and associated molecular signature occur in the human Parkinsonian brain in a region-specific manner

“…Nonetheless, the recent development of new MALDI systems where an oversampling approach is coupled with laser postionization (MALDI-2) is being optimized and was tested preliminarily in brain tissue, which might be the ideal strategy for follow-up studies ( 50 ). Furthermore, laser beams with lower diameters and increased resolution are being developed, potentially allowing for a more detailed mapping of such glycans in tissue sections in the future ( 51 ).…”

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

“…The scan resolution determines the spot (pixel) number measured by MS (with a spatial resolution down to 5–20 μm), while the MS resolution and accuracy determines the molecules that can be analyzed ( Aichler and Walch, 2015 ). It enables a label-free in situ characterization of hundreds of glycans on a single tissue section ( Hasan et al, 2021 ). The most common MS techniques employed in MALDI-MSI are FTICR for high-resolution analysis or TOF for rapid and high mass range analysis.…”