ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models.Acta neuropathologica communications · 2024Pooled it
- In vitro selection of VNAR antibodies using bioinformatics-based library design and cDNA display.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Amplification of seeding-competent tau aggregates by PMCA in human and experimental tauopathies.Acta neuropathologica communications · 2026Article
- Tau profiling of brain extracellular vesicles reveals PHF6 peptide as core for pathological tau seeding in Alzheimer's disease.Journal of biomedical science · 2026Article
- Nanobodies in biomedicine: from molecular characteristics to fabrication and clinical translation.Military Medical Research · 2026Review
- Nanobody Therapeutics in Alzheimer's Disease: From Molecular Mechanisms to Translational Approaches.Antibodies (Basel, Switzerland) · 2025Review
- Natural L-Hexapeptides with Therapeutic Potential for Alzheimer's Disease and Tauopathies.ACS omega · 2025Article
- Spontaneous pathology in PS19 tauopathy mice progresses via brain networks.Neurobiology of disease · 2025Article
- Beyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Anti-tau VHH therapy against PHF6: a safe approach to slowing the phenotype of tau pathology.Alzheimer's research & therapy · 2025Article
- AAV-mediated peripheral scFv's administration to reduce cerebral tau in adult P301S transgenic mice: Mono-vs. combination therapy.Molecular therapy. Methods & clinical development · 2025Article
- Incidental vs. Engineered Nanoparticles in Alzheimer's and Parkinson's Disease: Pathological Pathways and Therapeutic Interventions.Nano research · 2025Article
- Extracellular Vesicles Administered via Intrathecal Injection Mediate Safe Delivery of Nucleic Acids to the Central Nervous System for Gene Therapy.Journal of extracellular vesicles · 2025Article
- Structure-specific Mini-Prion Model for Alzheimer's Disease Tau Fibrils.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of tau neuronal internalization using anti-tau single domain antibodies.Nature communications · 2025Article
- Geometry based prediction of tau protein sites and motifs associated with misfolding and aggregation.Scientific reports · 2025Article
- Generation of nanobodies with conformational specificity for tau oligomers that recognize tau aggregates from human Alzheimer's disease samples.Biomaterials science · 2024Article
- Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.Journal of nanobiotechnology · 2024Review
- Anti-tau single domain antibodies clear pathological tau and attenuate its toxicity and related functional defects.Cell death & disease · 2024Article
- Single-Domain Antibodies as Antibody-Drug Conjugates: From Promise to Practice-A Systematic Review.Cancers · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tau proteins aggregate into filaments in brain cells in Alzheimer's disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic phage-display library of humanized VHHs was selected for its capacity to bind Tau microtubule-binding domain, composing the core of Tau fibrils. This parent VHH was optimized to improve its biochemical properties and to act in the intra-cellular compartment, resulting in VHH Z70. VHH Z70 precisely binds the PHF6 sequence, known for its nucleation capacity, as shown by the crystal structure of the complex. VHH Z70 was more efficient than the parent VHH to inhibit in vitro Tau aggregation in heparin-induced assays. Expression of VHH Z70 in a cellular model of Tau seeding also decreased the aggregation-reporting fluorescence signal. Finally, intra-cellular expression of VHH Z70 in the brain of an established tauopathy mouse seeding model demonstrated its capacity to mitigate accumulation of pathological Tau. VHH Z70, by targeting Tau inside brain neurons, where most of the pathological Tau resides, provides an immunological tool to target the intra-cellular compartment in tauopathies.
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