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A single domain antibody targeting Tau nucleation core inhibits Tau seeding
PUBLISHED April 08, 2023 (DOI: https://doi.org/10.54985/peeref.2304p3703739)
NOT PEER REVIEWED
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Authors
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Clément Danis1 , Elian Dupré1 , Orgeta Zejneli2 , Raphaëlle Caillierez2 , Alexis Arrial3 , Séverine Bégard2 , Anne Loyens2 , Justine Mortelecque1 , François-Xavier Cantrelle1 , Xavier Hanoulle1 , Jean-Christophe Rain4 , Morvane Colin2 , Luc Buée2 , Isabelle Landrieu1
- CNRS EMR9002 BSI Integrative Structural Biology, Lille, France
- Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Lille, Fr
- Hybrigenics services, Evry-Courcouronnes, France
- Hybrigenics Services, Evry-Courcouronnes, France
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Conference / event
- EuroTau meeting, November 2021 (Lille, France)
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Poster summary
- Tau proteins aggregate into filaments in brain cells in Alzheimer’s disease and related disorders named tauopathies. 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 VHH, named Z70, was efficient in inhibiting in vitro Tau fibrils assembly in heparin-induced assays. Expression of VHH Z70 in a cellular model of Tau seeding also decreased the fluorescence-reported signal. Finally, intracellular 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, provides a tool to explore the optimal strategies of immunotherapy in tauopathies.
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Keywords
- Nanobodies, Tau protein, Protein aggregation, Tauopathies, Tau fibrils, Immunotherapy
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Research areas
- Biological Sciences, Biochemistry, Neuroscience
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References
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- Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment. Danis C, Dupré E, Zejneli O, Caillierez R, Arrial A, Bégard S, Mortelecque J, Eddarkaoui S, Loyens A, Cantrelle FX, Hanoulle X, Rain JC, Colin M, Buée L, Landrieu I. Mol Ther. 2022 Apr 6;30(4):1484-1499. doi: 10.1016/j.ymthe.2022.01.009
- https://www.wwpdb.org/ with access code 7QCQ
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Funding
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- Agence nationale de la recherche ANR (No. ANR-11-LABX-01)
- Agence nationale de la recherche ANR (No. ANR-18-CE44-0016)
- European Union (No. Grant Agreement N° 305299)
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Supplemental files
- No data provided
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Additional information
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- Competing interests
- No competing interests were disclosed.
- Data availability statement
- The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.
- Creative Commons license
- Copyright © 2023 Danis et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Danis, C., Dupré, E., Zejneli, O., Caillierez, R., Arrial, A., Bégard, S., Loyens, A., Mortelecque, J., Cantrelle, F., Hanoulle, X., Rain, J., Colin, M., Buée, L., Landrieu, I. A single domain antibody targeting Tau nucleation core inhibits Tau seeding [not peer reviewed]. Peeref 2023 (poster).
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