Mass Spectrometry-Based Analysis of Serum N-Glycosylation Changes in Patients with Parkinson’s Disease

Xu, Mingming; Hong, Jing; Wu, Zhen; Han, Ying; Chen, Jing; Mao, Cheng‐Jie; Hao, Piliang; Zhang, Xumin; Liu, Chunfeng; Yang, Shuang

doi:10.1021/acschemneuro.2c00264

Cited by 26 publications

(22 citation statements)

References 45 publications

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“…In a recent N-glycoproteomics-based study, researchers identified an increase in the number of glycans containing core fucose, sialic acid, and bisecting N-acetylglucosamine in the sera of human patients, both at the overall glycan level and at specific glycosites of proteins related to Parkinson’s disease. These proteins include Ceruloplasmin, Haptoglobin, Kininogen-1, Complement Factor H, and Clusterin [ 68 ].…”

Section: N-glycosylationmentioning

confidence: 99%

Glycosylation and behavioral symptoms in neurological disorders

2023

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Glycosylation, the addition of glycans or carbohydrates to proteins, lipids, or other glycans, is a complex post-translational modification that plays a crucial role in cellular function. It is estimated that at least half of all mammalian proteins undergo glycosylation, underscoring its importance in the functioning of cells. This is reflected in the fact that a significant portion of the human genome, around 2%, is devoted to encoding enzymes involved in glycosylation. Changes in glycosylation have been linked to various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, and schizophrenia. Despite its widespread occurrence, the role of glycosylation in the central nervous system remains largely unknown, particularly with regard to its impact on behavioral abnormalities in brain diseases. This review focuses on examining the role of three types of glycosylation: N-glycosylation, O-glycosylation, and O-GlcNAcylation, in the manifestation of behavioral and neurological symptoms in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

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Section: N-glycosylationmentioning

confidence: 99%

Glycosylation and behavioral symptoms in neurological disorders

2023

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“… 1 Dynamic changes in glycosylation states have been associated with different disease processes, such as cancer, 2 viral infection responses, 3 and Alzheimer’s disease; 4 the extent of the glycosylation could be associated with the disease progression 5 and prognosis. 6 These observed associations indicate that the specific glycosylation states of proteins can be utilized as biomarkers for clinical diagnosis 7 and disease monitoring. 8 Currently, measurement of clinically adopted cancer protein biomarkers is mostly performed using affinity-based techniques.…”

Section: Introductionmentioning

confidence: 98%

“…Glycosylation is an important post-translational modification (PTM) mechanism of proteins, which modulates the protein function and is implicated in protein folding, trafficking, and cell-to-cell communications . Dynamic changes in glycosylation states have been associated with different disease processes, such as cancer, viral infection responses, and Alzheimer’s disease; the extent of the glycosylation could be associated with the disease progression and prognosis . These observed associations indicate that the specific glycosylation states of proteins can be utilized as biomarkers for clinical diagnosis and disease monitoring .…”

Section: Introductionmentioning

confidence: 99%

Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis

2022

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Elevated serum alpha-fetoprotein (AFP) can be observed in liver cirrhosis and hepatocellular carcinoma (HCC). The glycosylation patterns of AFP have been shown to differentiate these conditions, with AFP glycoforms with core fucosylation (AFP-L3) serving as a malignancy risk predictor for HCC. We have developed a method to detect endogenously present AFP proteoforms and to quantify the relative abundance of AFP-L3 glycoforms (AFP-L3%) in serum samples. This method consists of immune enrichment of endogenous AFP, followed by liquid chromatography coupled with high-resolution mass spectrometry (LC–HRMS) intact protein analysis of AFP. Data are available via ProteomeXchange with identifier PXD038606. Based on the AFP profiles in authentic patient serum samples, we have identified that the frequently observed AFP glycoforms without core fucosylation (AFP-L1) are G2S2 and G2S1, and common AFP-L3 glycoforms are G2FS1 and G2FS2. The intensities of glycoforms in the deconvoluted spectrum are used to quantify AFP-L3% in each sample. The method evaluation included reproducibility, specificity, dilution integrity, and comparison of AFP-L3% with a lectin-binding gel shift electrophoresis (GSE) assay. The AFP-L1 and AFP-L3 proteoforms were reproducibly identified in multiple patient serum samples, resulting in reproducible AFP-L3% quantification. There was considerable agreement between the developed LC–HRMS and commercial GSE methods when quantifying AFP-L3% (Pearson r = 0.63) with a proportional bias.

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“…Protein glycosylation is involved in almost all biological processes, such as protein-protein interaction, cell signaling, and immune response. 1,2 Abnormal glycosylation oen accompanies the occurrence and development of diseases, 3 such as autoimmune diseases, 4 diabetes, 5 cardiovascular diseases, 6 inammatory diseases, 7 viral infection, 8,9 neurodegenerative diseases, 10,11 and cancers. [12][13][14][15] Deciphering disease-specic glycosylation is an effective strategy to uncover the underlying causes of various diseases and identify biomarkers for diagnosis and prognosis.…”

Section: Introductionmentioning

confidence: 99%