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Cited by 211Glycosylation and Glycoproteins ResearchAlzheimer's disease research and treatmentsLysosomal Storage Disorders Research

Loss of O -GlcNAc glycosylation in forebrain excitatory neurons induces neurodegeneration

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Wang, Andrew C., Jensen, Elizabeth H., Rexach, Jessica E., Vinters, Harry V., Hsieh-Wilson, Linda C.·2016·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1606899113PMC PMC5206508
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Abstract

Significance: O -GlcNAcylation is an abundant posttranslational modification suggested to have both neuroprotective and neurodegenerative functions. Although previous studies on O -GlcNAc have illustrated its potential to modulate preexisting phenotypes in neurodegenerative animal models, the importance of O -GlcNAcylation in both the induction of neuropathology and the functioning of healthy adult neurons remained unclear. We generated a forebrain-specific O -GlcNAc transferase conditional knockout mouse and found that diminution of O -GlcNAc signaling induced progressive neurodegeneration in vivo, including pathogenic processing of tau and amyloid precursor protein, widespread neuronal death, gliosis, and memory loss. These results indicate that O -GlcNAcylation regulates pathways critical for neuronal health and survival and that modulating O -GlcNAc signaling may represent a neuroprotective strategy for neurodegenerative diseases.

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  • Decreased O-GlcNAcylation is associated with AD diagnosis and neurodegeneration.

    “This is particularly interesting since decreased O-GlcNAcylation is associated with AD diagnosis and neurodegeneration [48][49][50] .”

    From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [50]

    The paper reports that loss of OGT in adult mouse forebrain neurons causes progressive neurodegeneration. It also reports lower OGT protein expression in cortical neurons from patients with severe AD (Fig. 6), but it does not establish that O-GlcNAcylation itself is decreased in those patients; the human-brain results section notes prior reports of both increases and decreases in O-GlcNAcylated proteins. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Cited by

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Authors
Wang, A. C., Jensen, E. H., Rexach, J. E., Vinters, H. V., & Hsieh-Wilson, L. C.
Affiliations
  • California Institute of Technology (US)
  • University of California, Los Angeles (US)
  • Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2016-12-12
Volume
113
Issue
52
Pages
15120-15125
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1606899113
PMC
PMC5206508
OpenAlex
W2563045264
Cited by
211
References
6
Citations by year
2026: 17 · 2025: 21 · 2024: 25 · 2023: 27 · 2022: 13 · 2021: 30 · 2020: 28 · 2019: 18 · 2018: 11 · 2017: 21
FWCI
7.12
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor, 182 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health
  • National Defense Science and Engineering Graduate
  • National Institute on Aging (P50AG016570, RF1AG060540)
  • National Institute of General Medical Sciences (R01GM084724)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
O-GlcNAcylation, O-GlcNAc transferase, neurodegeneration, neuroinflammation, tau hyperphosphorylation, amyloid-beta, memory impairment, Alzheimer's disease, post-translational modification, neuronal cell death
MeSH terms
Acetylglucosamine, Alzheimer Disease, Animals, Brain Mapping, Crosses, Genetic, Female, Glycosylation, Hippocampus, Humans, Inflammation, Male, Memory Disorders, Mice, Inbred C57BL, Neuroglia, Neurons, Phosphorylation, Signal Transduction, Amyloid beta-Peptides, Prosencephalon, tau Proteins, N-Acetylglucosaminyltransferases, Mice, Knockout, Neurodegenerative Diseases, Mice

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