Neurodegenerative diseases have an essential impact on human lives with high mortality and poor prognosis in the early stage. Several biomarkers such as tau have been utilized to improve the prognosis of these diseases. However, the limited prediction accuracy is demanding to explore more reliable markers. Glycosylation is a common post-translational modification in mammalian cells and is involved in a variety of essential biological functions. Aberrant glycosylation and its isomeric distribution have been associated with many neurodegenerative diseases, including neurological disorders, Alzheimer’s disease, mild cognitive impairment and Parkinson’s disease. However, the glycomics and glycoproteomics methods for the isomeric glycans and glycopeptides for clinical samples remain a great challenge due to the complex microheterogeneity of glycoproteins. Over decades, different methods have been developed to facilitate the identification and quantitation of glycan and glycopeptide isomers. Coupling to a variety of separation techniques, mass spectrometry has been considered the most powerful tool in isomeric glycomics and glycoproteomics due to its high resolution, high sensitivity, and the ability to acquire sufficient structural information. Additionally, multiple sample preparation strategies and automated software were developed to improve the identification and quantitation accuracy and throughput for large clinical cohorts. During the past ten years, we have developed efficient methods for both glycomics and glycoproteomics isomeric analysis using C18-, porous graphitized carbon (PGC)-, mesoporous graphitized carbon (MGC)-, or micropillar array column (µPAC)-LC-MS/MS under different acquisition techniques, combined with several reliable sample derivatization and multiplexing strategies. Together, these advanced technologies and approaches enhance the pace of isomeric glycan and glycopeptide biomarker discovery. Here, we review recent glycomics and glycoproteomics methods for better isomeric characterization and their applications in neurodegenerative diseases.

Understanding the development and progression of neurodegenrative diseases by MS-Based glycomics and glycoproteomics

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ACS Fall 2022

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