ArticleNature chemistry2021
O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity.
Article in Nature chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 84 citations in OpenAlex.
- Loss of O-GlcNAc transferase activity impairs the dynamic formation of protective stress granules in ischemic cardiomyocytes.The Biochemical journal · 2026Article
- O-GlcNAcylation: A molecular switch linking brain health to neurodegeneration.Neural regeneration research · 2026Article
- Sweetening the bonds: how O-GlcNAcylation modulates cell adhesion.Acta pharmacologica Sinica · 2026Review
- Brain O-GlcNAcylation in Neurodegenerative Diseases: Context-Dependent Mechanisms and Precision Therapeutic Translation.Brain sciences · 2026Review
- Revealing and Exploiting the Biochemistry ofBiochemistry · 2026Review
- Protein O-GlcNAcylation in Health and Diseases.MedComm · 2025Review
- Targeting O-GlcNAcylation: Novel Therapeutic Strategies for Neurological Disease.Molecular neurobiology · 2025Review
- Advances in the chemical synthesis of human proteoforms.Science China. Life sciences · 2025Review
- O-GlcNAc modulation of nuclear pore complexes orchestrates mRNA export efficiency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Formation of a β-Endorphin Corona Mitigates Alzheimer's Amyloidogenesis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Effect of PHF-1 hyperphosphorylation on the seeding activity of C-terminal Tau fragments.Scientific reports · 2025Article
- Tissue-Specific Profiling ofBio-protocol · 2025Article
- Review
- O-GlcNAcylation-dependent liquid-liquid phase separation regulates the nuclear translocation of YAP to exacerbate vascular neointimal hyperplasia.Theranostics · 2025Article
- Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response.Israel journal of chemistry · 2024Article
- Altered glycosylation in cancer: molecular functions and therapeutic potential.Cancer communications (London, England) · 2024Review
- O-GlcNAc modification of HSP27 alters its protein interactions and promotes refolding of proteins through the BAG3/HSP70 co-chaperone.Protein science : a publication of the Protein Society · 2024Article
- O-GlcNAc Modification of α-Synuclein Can Alter Monomer Dynamics to Control Aggregation Kinetics.ACS chemical neuroscience · 2024Article
- Potential for targeting small heat shock protein modifications.Trends in pharmacological sciences · 2024Article
- Advancing Renal Amyloidosis Care: The Role of Modern Diagnostic Techniques with the Potential of Enhancing Patient Outcomes.International journal of molecular sciences · 2024Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
A major role for the intracellular post-translational modification O-GlcNAc appears to be the inhibition of protein aggregation. Most of the previous studies in this area focused on O-GlcNAc modification of the amyloid-forming proteins themselves. Here we used synthetic protein chemistry to discover that O-GlcNAc also activates the anti-amyloid activity of certain small heat shock proteins (sHSPs), a potentially more important modification event that can act broadly and substoichiometrically. More specifically, we found that O-GlcNAc increases the ability of sHSPs to block the amyloid formation of both α-synuclein and Aβ(1-42). Mechanistically, we show that O-GlcNAc near the sHSP IXI-domain prevents its ability to intramolecularly compete with substrate binding. Finally, we found that, although O-GlcNAc levels are globally reduced in Alzheimer's disease brains, the modification of relevant sHSPs is either maintained or increased, which suggests a mechanism to maintain these potentially protective O-GlcNAc modifications. Our results have important implications for neurodegenerative diseases associated with amyloid formation and potentially other areas of sHSP biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.