ArticleEMBO reports2021
O-GlcNAcylation of TDP-43 suppresses proteinopathies and promotes TDP-43's mRNA splicing activity.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- O-GlcNAcylation: A molecular switch linking brain health to neurodegeneration.Neural regeneration research · 2026Article
- Brain O-GlcNAcylation in Neurodegenerative Diseases: Context-Dependent Mechanisms and Precision Therapeutic Translation.Brain sciences · 2026Review
- Cross-talk between glycosylation pathways: Mechanistic insights and implications for human diseases.Molecular metabolism · 2026Review
- Protein O-GlcNAcylation in Health and Diseases.MedComm · 2025Review
- Targeting O-GlcNAcylation: Novel Therapeutic Strategies for Neurological Disease.Molecular neurobiology · 2025Review
- O-GlcNAcylation of nuclear proteins in the mouse liver exhibit daily oscillations that are influenced by meal timing.PLoS biology · 2025Article
- Methylome analysis of FTLD patients with TDP-43 pathology identifies epigenetic signatures specific to pathological subtypes.Molecular neurodegeneration · 2025Article
- Mealtime alters daily rhythm in nuclear O-GlcNAc proteome to regulate hepatic gene expression.bioRxiv : the preprint server for biology · 2025Article
- Brain O-GlcNAcylation: Bridging physiological functions, disease mechanisms, and therapeutic applications.Molecular psychiatry · 2025Review
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.Acta neuropathologica communications · 2024Review
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells.Neuromolecular medicine · 2024Article
- Tissue-specificeLife · 2024Article
- Understanding and exploiting the roles of O-GlcNAc in neurodegenerative diseases.The Journal of biological chemistry · 2023Review
- Glycosylation and behavioral symptoms in neurological disorders.Translational psychiatry · 2023Review
- Combining Selective Enrichment and a Boosting Approach to Globally and Site-Specifically Characterize Protein Co-translationalAnalytical chemistry · 2023Article
- Chemical Biology Approaches to Understanding Neuronal O-GlcNAcylation.Israel journal of chemistry · 2023Article
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Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
Pathological TDP-43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP); however, how TDP-43 aggregation and function are regulated remain poorly understood. Here, we show that O-GlcNAc transferase OGT-mediated O-GlcNAcylation of TDP-43 suppresses ALS-associated proteinopathies and promotes TDP-43's splicing function. Biochemical and cell-based assays indicate that OGT's catalytic activity suppresses TDP-43 aggregation and hyperphosphorylation, whereas abolishment of TDP-43 O-GlcNAcylation impairs its RNA splicing activity. We further show that TDP-43 mutations in the O-GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP-43 overexpression in Drosophila motor neurons. We finally demonstrate that O-GlcNAcylation of TDP-43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O-GlcNAcylation might be a target for the treatment of TDP-43-linked pathogenesis.
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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 OpenQuestion graph.