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Cited by 33Glycosylation and Glycoproteins ResearchProteoglycans and glycosaminoglycans researchNeuroscience and Neuropharmacology Research

Brain O-GlcNAcylation: Bridging physiological functions, disease mechanisms, and therapeutic applications

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Chen, Liping, Jiang, Huihui, Licinio, Julio, Wu, Haitao·2025·Molecular Psychiatry
DOI 10.1038/s41380-025-02943-zPMC PMC12092303
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Abstract

O-GlcNAcylation, a dynamic post-translational modification occurring on serine or threonine residues of numerous proteins, plays a pivotal role in various cellular processes, including gene regulation, metabolism, and stress response. Abundant in the brain, O-GlcNAcylation intricately governs neurodevelopment, synaptic assembly, and neuronal functions. Recent investigations have established a correlation between the dysregulation of brain O-GlcNAcylation and a broad spectrum of neurological disorders and injuries, spanning neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as injuries to the central nervous system (CNS). Manipulating O-GlcNAcylation has demonstrated neuroprotective properties against these afflictions. This review delineates the roles and mechanisms of O-GlcNAcylation in the CNS under both physiological and pathological circumstances, with a focus on its neuroprotective effects in neurological disorders and injuries. We discuss the involvement of O-GlcNAcylation in key processes such as neurogenesis, synaptic plasticity, and energy metabolism, as well as its implications in conditions like Alzheimer's disease, Parkinson's disease, and ischemic stroke. Additionally, we explore prospective therapeutic approaches for CNS disorders and injuries by targeting O-GlcNAcylation, highlighting recent clinical developments and future research directions. This comprehensive overview aims to provide insights into the potential of O-GlcNAcylation as a therapeutic target and guide future investigations in this promising field.

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Cited by

Sorted by citations

Authors
Chen, L., Jiang, H., Licinio, J., & Wu, H.
Affiliations
  • Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN)
  • Nantong University (CN)
Corresponding author
Wu, Haitao
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2025-03-03
Volume
30
Issue
6
Pages
2754-2772
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-025-02943-z
PMC
PMC12092303
OpenAlex
W4408113458
Cited by
33
References
9
Citations by year
2026: 23 · 2025: 10
FWCI
2.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (32171148)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
O-GlcNAcylation, post-translational modification, brain, neuroprotection, brain development, synaptic plasticity, neurogenesis, neuronal energy metabolism, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, ischemic stroke, central nervous system injury, neurological disorders, therapeutic target
MeSH terms
Acetylglucosamine, Animals, Brain, Glycosylation, Humans, Neuronal Plasticity, Neurons, Protein Processing, Post-Translational, Neurodegenerative Diseases, Neurogenesis

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