ArticleThe Journal of clinical investigation2023
Monoclonal antibody Y01 prevents tauopathy progression induced by lysine 280-acetylated tau in cell and mouse models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- NDST3 suppression restores lysosomal acidification and ameliorates amyloid-β and MAPT/tau pathology in Alzheimer's disease.Translational neurodegeneration · 2026Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- REV-ERBα regulates brain NADNature aging · 2025Article
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
- Decoding tau acetylation in Alzheimer's disease and tauopathies: from site-specific mechanisms to therapeutic horizons.BMB reports · 2025Review
- The Role and Pathogenesis of Tau Protein in Alzheimer's Disease.Biomolecules · 2025Review
- Revisiting the therapeutic landscape of tauopathies: assessing the current pipeline and clinical trials.Alzheimer's research & therapy · 2025Review
- Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.ACS omega · 2025Review
- Development and characterization of novel anti-acetylated tau monoclonal antibodies to probe pathogenic tau species in Alzheimer's disease.Acta neuropathologica communications · 2024Article
- Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.International journal of molecular sciences · 2024Review
- Anti-acetylated-tau immunotherapy is neuroprotective in tauopathy and brain injury.Molecular neurodegeneration · 2024Article
- Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review.Molecules (Basel, Switzerland) · 2024Review
- Single-domain antibodies and aptamers drive new opportunities for neurodegenerative disease research.Frontiers in immunology · 2024Review
- Human tauopathy strains defined by phosphorylation in R1-R2 repeat domains of tau.Acta neuropathologica communications · 2023Article
- Application of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Disease-associated patterns of acetylation stabilize tau fibril formation.Structure (London, England : 1993) · 2023Article
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spatiotemporal pattern of the spread of pathologically modified tau through brain regions in Alzheimer's disease (AD) can be explained by prion-like cell-to-cell seeding and propagation of misfolded tau aggregates. Hence, to develop targeted therapeutic antibodies, it is important to identify the seeding- and propagation-competent tau species. The hexapeptide 275VQIINK280 of tau is a critical region for tau aggregation, and K280 is acetylated in various tauopathies, including AD. However, the mechanism that links tau acetylated on lysine 280 (tau-acK280) to subsequent progression to neurodegenerative disease remains unclear. Here, we demonstrate that tau-acK280 is critical for tau propagation processes including secretion, aggregation, and seeding. We developed an antibody, Y01, that specifically targets tau-acK280 and solved the crystal structure of Y01 in complex with an acK280 peptide. The structure confirmed that Y01 directly recognizes acK280 and the surrounding residues. Strikingly, upon interaction with acetylated tau aggregates, Y01 prevented tauopathy progression and increased neuronal viability in neuron cultures and in tau-Tg mice through antibody-mediated neutralization and phagocytosis, respectively. Based on our observations that tau-acK280 is a core species involved in seeding and propagation activities, the Y01 antibody that specifically recognizes acK280 represents a promising therapeutic candidate for AD and other neurodegenerative diseases associated with tauopathy.
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