PreprintCited by 13Glycosylation and Glycoproteins ResearchAdvanced Proteomics Techniques and ApplicationsRedox biology and oxidative stress

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Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases

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Fang, Pan, Yu, Xiangming, Ding, MengYang, Cong, Qifei, Jiang, Hongyu, Shi, Qi, Zhao, Weiwei, Zheng, Weimin, Li, Yingning, Ling, Zixiang, Kong, Wei-Jun, Yang, Pengyuan, Shen, Huali·2025·Nature Communications

Preprint — published as 10.1038/s41467-025-60437-6

Abstract

The current depth of site-specific N-glycoproteomics is insufficient to fully characterize glycosylation events in biological samples. Herein, we achieved an ultradeep and precision analysis of the N-glycoproteome of mouse tissues by integrating multiple workflows. The largest N-glycoproteomic dataset to date was established on mice, which contained 91,972 precursor glycopeptides, 62,216 glycoforms, 8,939 glycosites and 4,563 glycoproteins. The database consisted of 6.8 million glyco-spectra (containing oxonium ions), among which 160,928 were high-quality spectra with confident N-glycopeptide identifications. The large-scale and high-quality dataset enhanced the performance of current artificial intelligence models for glycopeptide tandem spectrum prediction. Using this ultradeep dataset, we observed tissue specific microheterogeneity and functional implications of protein glycosylation in mice. Furthermore, the region-resolved brain N-glycoproteomes for Alzheimer’s Diseases, Parkinson Disease and aging mice revealed the spatiotemporal signatures and distinct pathological functions of the N-glycoproteins. A comprehensive database resource of experimental N-glycoproteomic data from this study and previous literatures were further established. This N-glycoproteome atlas serves as a promising tool for revealing the role of protein glycosylation in biological systems.

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Metadata

Authors
Fang, P., Yu, X., Ding, M., Cong, Q., Jiang, H., Shi, Q., Zhao, W., Zheng, W., Li, Y., Ling, Z., Kong, W.-J., Yang, P., & Shen, H.
Affiliations
  • Soochow University (CN)
  • Shanghai Medical College of Fudan University (CN)
  • Second Affiliated Hospital of Soochow University (CN)
  • The Affiliated Taizhou People's Hospital of Nanjing Medical University (CN)
  • Tongji University (CN)
  • Fudan University (CN)
Corresponding author
  • Fang, Pan
  • Shen, Huali
Venue
Nature Communications
Publisher
openRxiv
Published
2025-02-19
Volume
16
Issue
1
Pages
5568-5568
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4411887142
Cited by
13
References
1
Citations by year
2026: 7 · 2025: 6
FWCI
3.88
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81827901, 32200778, 22201217, 82272174, 62475179, 32101026, 2022ZD0211600, 32471014)
  • Government of Jiangsu Province
  • Science and Technology Commission of Shanghai Municipality (22S31901900)
  • Ministry of Education, India
  • Natural Science Foundation of Jiangsu Province (BK20220494)
  • Soochow University
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
  • National Key Research and Development Program of China (2021YFA1301601, 2022YFC2503904)
  • Second Affiliated Hospital of Soochow University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
N-glycoproteome, protein glycosylation, mouse tissues, brain aging, Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, glycopeptide identification, glycoforms
MeSH terms
Aging, Alzheimer Disease, Animals, Brain, Glycopeptides, Glycoproteins, Glycosylation, Humans, Male, Mice, Inbred C57BL, Parkinson Disease, Neurodegenerative Diseases, Proteome, Databases, Protein, Proteomics, Mice

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