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Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment

Danis, Clément, Dupré, Elian, Zejneli, Orgeta, Caillierez, Raphaëlle, Arrial, Alexis, Bégard, Séverine, Mortelecque, Justine, Eddarkaoui, Sabiha, Loyens, Anne, Cantrelle, François-Xavier, Hanoulle, Xavier, Rain, Jean-Christophe, Colin, Morvane, Buée, Luc, Landrieu, Isabelle·2022·Molecular Therapy
DOI 10.1016/j.ymthe.2022.01.009PMC PMC9077319

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Graphical abstract CC BY-NC-ND · PubMed Central
Figure 1 VHH E4-1 binds to the MTBD of Tau (A) Overlay of 1H, 15N HSQC two-dimensional full spectra and enlargements of free full-length Tau2N4R (in red) or Tau2N4R mixed with non-labeled VHH E4-1 (in blue) (n = 1). In the spectrum of Tau in the presence of VHH E4-1, multiple resonances are broadened beyond detection compared with the Tau control spectrum. (B) Normalized NMR intensities (I/I0) along the Tau sequence with (I0) and (I) corresponding to the resonance intensity when Tau is free in solution or mixed with equimolar quantity of VHH E4-1 (I), respectively. The normalized intensity ratios (I/I0) plot allowed the identification of the Tau MTBD domain as the target of VHH E4-1 interaction. A red double-arrow indicates the region containing the corresponding major broadened resonances, which was mapped to the R2-R3 repeats in the MTBD. N1 and N2 are two inserted sequences in the N-terminal domain (1–163) that are not present in all Tau isoforms (named Tau 0N, Tau 1N or Tau 2N), the proline-rich domain is subdivided in P1 and P2 regions, the MTBD consists of four partially repeated regions, R1 to R4 (in Tau 4R). The R2 repeat is not present in Tau 3R. C-ter is for the C-terminal domain.
Figure 1 VHH E4-1 binds to the MTBD of Tau (A) Overlay of 1H, 15N HSQC two-dimensional full spectra and enlargements of free full-length Tau2N4R (in red) or Tau2N4R mixed with non-labeled VHH E4-1 (in blue) (n = 1). In the spectrum of Tau in the presence of VHH E4-1, multiple resonances are broadened beyond detection compared with the Tau control spectrum. (B) Normalized NMR intensities (I/I0) along the Tau sequence with (I0) and (I) corresponding to the resonance intensity when Tau is free in solution or mixed with equimolar quantity of VHH E4-1 (I), respectively. The normalized intensity ratios (I/I0) plot allowed the identification of the Tau MTBD domain as the target of VHH E4-1 interaction. A red double-arrow indicates the region containing the corresponding major broadened resonances, which was mapped to the R2-R3 repeats in the MTBD. N1 and N2 are two inserted sequences in the N-terminal domain (1–163) that are not present in all Tau isoforms (named Tau 0N, Tau 1N or Tau 2N), the proline-rich domain is subdivided in P1 and P2 regions, the MTBD consists of four partially repeated regions, R1 to R4 (in Tau 4R). The R2 repeat is not present in Tau 3R. C-ter is for the C-terminal domain.CC BY-NC-ND · PubMed Central
Figure 2 VHH Z70 is optimized for intra-cellular binding and has a better affinity for Tau than VHH E4-1 (A) Results from yeast two-hybrid. A growth test on nonselective medium (left panel, lacking only leucine and tryptophan) or on selective medium (right panel, lacking leucine, tryptophan and histidine) was performed with dilution (top to bottom) of the diploid yeast culture expressing both bait and prey constructs. Positive and negative controls of interaction consist respectively of Smad/Smurf interaction42 and Tau alone (empty vector). VHH E4-1 did not interact with Tau in yeast (no growth on selective medium) whereas VHH Z70 did. (B) Domain organization of the VHHs (CDR are for complementarity-determining regions and FR for framework regions) and sequence alignment between VHH E4-1 and VHH Z70 showing four mutations in the FR: G12V, P16S, T81M, and W114G. (C, D) HEK293 cells were transfected with plasmid encoding either (C) mCherry-VHH E4.1 or (D) mCherry-VHH Z70 and mCherry or mCherry VHH anti-GFP (Figure S4). mCherry is visualized in red and nuclei in blue. The scale bar is indicated on the figure. (E) Percentage of mCherry positive cells with puncta is provided for 10 images per group and three independent experiments (30 points). Error bars indicate mean and SD of the data. ∗∗∗∗ correspond to a p value < 0.0001. (F, G) Sensorgrams (reference subtracted data) of single cycle kinetics analysis performed on immobilized biotinylated Tau, with five injections of (F) VHH E4-1 or (G) VHH Z70 at 0.125 μM, 0.25 μM, 0.5 μM, 1 μM, and 2 μM (n = 1). Dissociation equilibrium constant Kd were calculated from the ratio of off-rate and on-rate kinetic constants koff/kon. kon, koff, and Kd are included in the table in Figure S7. Black lines correspond to the fitted curves, red lines to the measurements.
Figure 2 VHH Z70 is optimized for intra-cellular binding and has a better affinity for Tau than VHH E4-1 (A) Results from yeast two-hybrid. A growth test on nonselective medium (left panel, lacking only leucine and tryptophan) or on selective medium (right panel, lacking leucine, tryptophan and histidine) was performed with dilution (top to bottom) of the diploid yeast culture expressing both bait and prey constructs. Positive and negative controls of interaction consist respectively of Smad/Smurf interaction42 and Tau alone (empty vector). VHH E4-1 did not interact with Tau in yeast (no growth on selective medium) whereas VHH Z70 did. (B) Domain organization of the VHHs (CDR are for complementarity-determining regions and FR for framework regions) and sequence alignment between VHH E4-1 and VHH Z70 showing four mutations in the FR: G12V, P16S, T81M, and W114G. (C, D) HEK293 cells were transfected with plasmid encoding either (C) mCherry-VHH E4.1 or (D) mCherry-VHH Z70 and mCherry or mCherry VHH anti-GFP (Figure S4). mCherry is visualized in red and nuclei in blue. The scale bar is indicated on the figure. (E) Percentage of mCherry positive cells with puncta is provided for 10 images per group and three independent experiments (30 points). Error bars indicate mean and SD of the data. ∗∗∗∗ correspond to a p value < 0.0001. (F, G) Sensorgrams (reference subtracted data) of single cycle kinetics analysis performed on immobilized biotinylated Tau, with five injections of (F) VHH E4-1 or (G) VHH Z70 at 0.125 μM, 0.25 μM, 0.5 μM, 1 μM, and 2 μM (n = 1). Dissociation equilibrium constant Kd were calculated from the ratio of off-rate and on-rate kinetic constants koff/kon. kon, koff, and Kd are included in the table in Figure S7. Black lines correspond to the fitted curves, red lines to the measurements.CC BY-NC-ND · PubMed Central
Figure 3 The PHF6 peptide sequence is essential for VHH Z70 binding to Tau MTBD (A) Sensorgram (reference subtracted data) of single-cycle kinetics analysis performed on immobilized biotinylated VHH Z70, with five injections of peptide Tau[273–318] fused at its N-terminus with the SUMO protein (n = 1) at 31.25 nM, 62.5 nM, 125 nM, 250 nM, and 500 nM. Tau peptide sequence and, kon, koff, and Kd are included in the table in Figure S7. Black lines correspond to the fitted curves, red lines to the measurements. (B) Results from yeast two-hybrid. The VHH are expressed as preys, with a C-terminal Gal4-activation domain fusion (VHH-Gal4AD) and Tau0N4R/MTBD as bait with a C-terminal fusion with lexA (Tau0N4R/MTBD-LexA). A growth test on nonselective medium (upper panel Growth, lacking only leucine and tryptophane) or on selective medium (lower panel Interaction, lacking leucine, tryptophane, and histidine) was performed of the diploid yeast culture expressing both bait and prey constructs. Positive and negative controls of interaction consist respectively in Smad/Smurf interaction and Tau or chimeric MTBD alone (empty vector). (C) Ribbon representation of the crystal structure of the complex between VHH Z70 and the PHF6 peptide. The CDR1, CDR2, and CDR3 loops of VHH 70 are colored in pink, in dark blue, and in red, respectively. Framework regions of the VHH are represented in green and the PHF6 Tau peptide in cyan. The right panel shows the five intermolecular H-bonds (dashed blue lines) between VHH Z70 and Tau peptide. See Figure S11 for 90°-rotation view and surface representation.
Figure 3 The PHF6 peptide sequence is essential for VHH Z70 binding to Tau MTBD (A) Sensorgram (reference subtracted data) of single-cycle kinetics analysis performed on immobilized biotinylated VHH Z70, with five injections of peptide Tau[273–318] fused at its N-terminus with the SUMO protein (n = 1) at 31.25 nM, 62.5 nM, 125 nM, 250 nM, and 500 nM. Tau peptide sequence and, kon, koff, and Kd are included in the table in Figure S7. Black lines correspond to the fitted curves, red lines to the measurements. (B) Results from yeast two-hybrid. The VHH are expressed as preys, with a C-terminal Gal4-activation domain fusion (VHH-Gal4AD) and Tau0N4R/MTBD as bait with a C-terminal fusion with lexA (Tau0N4R/MTBD-LexA). A growth test on nonselective medium (upper panel Growth, lacking only leucine and tryptophane) or on selective medium (lower panel Interaction, lacking leucine, tryptophane, and histidine) was performed of the diploid yeast culture expressing both bait and prey constructs. Positive and negative controls of interaction consist respectively in Smad/Smurf interaction and Tau or chimeric MTBD alone (empty vector). (C) Ribbon representation of the crystal structure of the complex between VHH Z70 and the PHF6 peptide. The CDR1, CDR2, and CDR3 loops of VHH 70 are colored in pink, in dark blue, and in red, respectively. Framework regions of the VHH are represented in green and the PHF6 Tau peptide in cyan. The right panel shows the five intermolecular H-bonds (dashed blue lines) between VHH Z70 and Tau peptide. See Figure S11 for 90°-rotation view and surface representation.CC BY-NC-ND · PubMed Central
Figure 4 VHH E4-1 and VHH Z70 inhibit in vitro Tau aggregation Aggregation of Tau (10 μM) in the absence of heparin (black curve), in the presence of heparin and of increasing concentration of (A) VHH F8-2, (B) VHH E4-1, and (C) VHH Z70 (0, 1, 2.5, 5, and 10 μM) monitored by Thioflavin T fluorescence at 490 nm (n = 3). Error bars: SEM.
Figure 4 VHH E4-1 and VHH Z70 inhibit in vitro Tau aggregation Aggregation of Tau (10 μM) in the absence of heparin (black curve), in the presence of heparin and of increasing concentration of (A) VHH F8-2, (B) VHH E4-1, and (C) VHH Z70 (0, 1, 2.5, 5, and 10 μM) monitored by Thioflavin T fluorescence at 490 nm (n = 3). Error bars: SEM.CC BY-NC-ND · PubMed Central
Figure 5 VHH Z70 blocks intra-cellular seeding of Tau MTBD in HEK293 biosensor cells (A and B) Analysis of Tau seeding in HEK293 Tau RD P301S FRET Biosensor cells. (A) Percentage of FRET positive cells in the whole population determined from flow cytometry data for cells transfected with vehicle or transfected with vehicle and VHH F8-2 followed by MTBD seeds (n = 3). (B) Percentage of FRET positive cells in the mCherry-gated population determined from flow cytometry data for cells transfected with VHH F8-2, VHH E4-1, and VHH Z70 followed by MTBD seeds (n = 3). A significant decrease of FRET signal, reporting a decrease intra-cellular MTBD aggregation, is observed in the presence of VHH Z70. ∗p value <0.05, ∗∗∗p value < 0.001, ns, not significant. Error bars: SEM.
Figure 5 VHH Z70 blocks intra-cellular seeding of Tau MTBD in HEK293 biosensor cells (A and B) Analysis of Tau seeding in HEK293 Tau RD P301S FRET Biosensor cells. (A) Percentage of FRET positive cells in the whole population determined from flow cytometry data for cells transfected with vehicle or transfected with vehicle and VHH F8-2 followed by MTBD seeds (n = 3). (B) Percentage of FRET positive cells in the mCherry-gated population determined from flow cytometry data for cells transfected with VHH F8-2, VHH E4-1, and VHH Z70 followed by MTBD seeds (n = 3). A significant decrease of FRET signal, reporting a decrease intra-cellular MTBD aggregation, is observed in the presence of VHH Z70. ∗p value <0.05, ∗∗∗p value < 0.001, ns, not significant. Error bars: SEM.CC BY-NC-ND · PubMed Central
Figure 6 VHH Z70 reduces human Tau seeding activity induced by h-AD brain-derived material in THY-tau30 Tg mouse model (A) Bilateral intra-cranial injection of LVs to express either VHH anti-GFP or VHH Z70 was performed in 1-month-old THY-tau30 mice. Induction of the tauopathy occurred by a second bilateral injection, at the same coordinates, 15 days after with human h-AD. Mice were killed and perfused 1 month later (aged 2.5 months). (B) The whole brain was processed for immunohistochemical analysis using AT8 for the control group (labeled VHH anti-GFP + AD; n = 9) corresponding to injection of LVs VHH anti-GFP followed by h-AD injection and the group (labeled VHH Z70 + AD; n = 7) corresponding to LVs VHH Z70 followed by h-AD injection. Enlarged images are taken from the hippocampus (injection site, AP: −2.46). Scale bars are indicated on the figure. (C) Each data point corresponds to the quantification for one hemisphere. Results are presented as AT8 immunoreactivity (immunoreactive area normalized to the whole area). ∗p value <0.05. Error bars: SD. (D) In a region of the hippocampus (molecular layer) with strong induction of the pathology (detected using AT-8 antibodies, visualized in red, see VHH anti-GFP + AD) and good diffusion of LVs expressing Z70 (detected using mCherry antibodies, visualized in green, see VHH Z70 + AD), there is almost no Tau pathology (red labeling) in neurons positive for VHH-Z70 expression (green labeling). Immunohistochemical analysis is shown for two animals (VHH Z70 + AD) with different levels of pathology. Larger views of the analysis are shown in Figure S16.
Figure 6 VHH Z70 reduces human Tau seeding activity induced by h-AD brain-derived material in THY-tau30 Tg mouse model (A) Bilateral intra-cranial injection of LVs to express either VHH anti-GFP or VHH Z70 was performed in 1-month-old THY-tau30 mice. Induction of the tauopathy occurred by a second bilateral injection, at the same coordinates, 15 days after with human h-AD. Mice were killed and perfused 1 month later (aged 2.5 months). (B) The whole brain was processed for immunohistochemical analysis using AT8 for the control group (labeled VHH anti-GFP + AD; n = 9) corresponding to injection of LVs VHH anti-GFP followed by h-AD injection and the group (labeled VHH Z70 + AD; n = 7) corresponding to LVs VHH Z70 followed by h-AD injection. Enlarged images are taken from the hippocampus (injection site, AP: −2.46). Scale bars are indicated on the figure. (C) Each data point corresponds to the quantification for one hemisphere. Results are presented as AT8 immunoreactivity (immunoreactive area normalized to the whole area). ∗p value <0.05. Error bars: SD. (D) In a region of the hippocampus (molecular layer) with strong induction of the pathology (detected using AT-8 antibodies, visualized in red, see VHH anti-GFP + AD) and good diffusion of LVs expressing Z70 (detected using mCherry antibodies, visualized in green, see VHH Z70 + AD), there is almost no Tau pathology (red labeling) in neurons positive for VHH-Z70 expression (green labeling). Immunohistochemical analysis is shown for two animals (VHH Z70 + AD) with different levels of pathology. Larger views of the analysis are shown in Figure S16.CC BY-NC-ND · PubMed Central

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Cites

Research works printed but not linked: 68

  1. Messer, 2020, Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders, Neurobiol. Dis., 134, 104619, 10.1016/j.nbd.2019.104619 · DOI
  2. Goedert, 2006, A century of Alzheimer's disease, Science, 314, 777, 10.1126/science.1132814 · DOI
  3. Brion, 1986, Alzheimer's disease and tau proteins, Lancet, 2, 1098, 10.1016/S0140-6736(86)90495-2 · DOI
  4. Grundke-Iqbal, 1986, Microtubule-associated protein tau. A component of Alzheimer paired helical filaments, J. Biol. Chem., 261, 6084, 10.1016/S0021-9258(17)38495-8 · DOI
  5. Mudher, 2017, What is the evidence that tau pathology spreads through prion-like propagation?, Acta Neuropathol. Commun., 5, 99, 10.1186/s40478-017-0488-7 · DOI · Paper page
  6. Wilcock, 1982, Plaques, tangles and dementia. A quantitative study, J. Neurol. Sci., 56, 343, 10.1016/0022-510X(82)90155-1 · DOI · Paper page
  7. Boutajangout, 2010, Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model, J. Neurosci., 30, 16559, 10.1523/JNEUROSCI.4363-10.2010 · DOI · Paper page
  8. Dai, 2017, Tau passive immunization inhibits not only tau but also Aβ pathology, Alzheimers Res. Ther., 9, 1, 10.1186/s13195-016-0227-5 · DOI
  9. Chai, 2011, Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression, J. Biol. Chem., 286, 34457, 10.1074/jbc.M111.229633 · DOI
  10. Yanamandra, 2013, Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo, Neuron, 80, 402, 10.1016/j.neuron.2013.07.046 · DOI · Paper page
  11. Albert, 2019, Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody, Brain, 142, 1736, 10.1093/brain/awz100 · DOI
  12. Jadhav, 2019, A walk through tau therapeutic strategies, Acta Neuropathol. Commun., 7, 22, 10.1186/s40478-019-0664-z · DOI
  13. Dujardin, 2014, Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies, Acta Neuropathol. Commun., 2, 14, 10.1186/2051-5960-2-14 · DOI
  14. Colin, 2020, From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy, Acta Neuropathol., 139, 3, 10.1007/s00401-019-02087-9 · DOI · Paper page
  15. Clavaguera, 2014, Intercellular transfer of tau aggregates and spreading of tau pathology: implications for therapeutic strategies, Neuropharmacology, 76, 9, 10.1016/j.neuropharm.2013.08.037 · DOI
  16. Dujardin, 2014, Ectosomes: a new mechanism for non-exosomal secretion of tau protein, PLoS One, 9, e100760, 10.1371/journal.pone.0100760 · DOI
  17. Leroux, 2021, Extracellular vesicles: major actors of heterogeneity in tau spreading among human tauopathies, Mol. Ther. J. Am. Soc. Gene Ther.
  18. Tardivel, 2016, Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies, Acta Neuropathol. Commun., 4, 117, 10.1186/s40478-016-0386-4 · DOI · Paper page
  19. Pain, 2015, Camelid single-domain antibody fragments: uses and prospects to investigate protein misfolding and aggregation, and to treat diseases associated with these phenomena, Biochimie, 111, 82, 10.1016/j.biochi.2015.01.012 · DOI
  20. Herce, 2017, Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells, Nat. Chem., 9, 762, 10.1038/nchem.2811 · DOI
  21. Li, 2016, Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging, FASEB J., 26, 3969, 10.1096/fj.11-201384 · DOI
  22. Gormal, 2020, Modular transient nanoclustering of activated β2-adrenergic receptors revealed by single-molecule tracking of conformation-specific nanobodies, Proc. Natl. Acad. Sci. U S A, 117, 30476, 10.1073/pnas.2007443117 · DOI
  23. Li, 2016, Camelid single-domain antibodies: a versatile tool for in vivo imaging of extracellular and intracellular brain targets, J. Control Release, 243, 1, 10.1016/j.jconrel.2016.09.019 · DOI
  24. Vitale, 2018, Anti-tau conformational scFv MC1 antibody efficiently reduces pathological tau species in adult JNPL3 mice, Acta Neuropathol. Commun., 6, 82, 10.1186/s40478-018-0585-2 · DOI
  25. Goodwin, 2020, Anti-tau scFvs targeted to the cytoplasm or secretory pathway variably modify pathology and neurodegenerative phenotypes, Mol. Ther. J. Am. Soc. Gene Ther.
  26. von Bergen, 2000, Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure, Proc. Natl. Acad. Sci. U S A, 97, 5129, 10.1073/pnas.97.10.5129 · DOI · Paper page
  27. Moutel, 2016, NaLi-H1: a universal synthetic library of humanized nanobodies providing highly functional antibodies and intrabodies, eLife, 5, e16228, 10.7554/eLife.16228 · DOI
  28. Dupré, 2019, Single domain antibody fragments as new tools for the detection of neuronal tau protein in cells and in mice studies, ACS Chem. Neurosci., 10, 3997, 10.1021/acschemneuro.9b00217 · DOI
  29. Dingus, 2021, A general approach for stabilizing nanobodies for intracellular expression, biorxiv
  30. Vielemeyer, 2010, Characterization of single chain antibody targets through yeast two hybrid, BMC Biotechnol., 10, 59, 10.1186/1472-6750-10-59 · DOI
  31. Zhang, 2001, Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase, Proc. Natl. Acad. Sci. U S A, 98, 974, 10.1073/pnas.98.3.974 · DOI
  32. Holmes, 2014, Proteopathic tau seeding predicts tauopathy in vivo, Proc. Natl. Acad. Sci. U S A, 111, E4376, 10.1073/pnas.1411649111 · DOI · Paper page
  33. Vandermeeren, 2018, Anti-tau monoclonal antibodies derived from soluble and filamentous tau show diverse functional properties in vitro and in vivo, J. Alzheimers Dis., 65, 265, 10.3233/JAD-180404 · DOI
  34. Malia, 2016, Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti-tau antibody AT8, Proteins, 84, 427, 10.1002/prot.24988 · DOI
  35. Gallardo, 2019, Targeting tauopathy with engineered tau-degrading intrabodies, Mol. Neurodegener., 14, 38, 10.1186/s13024-019-0340-6 · DOI
  36. Nobuhara, 2017, Tau antibody-targeting pathological species block neuronal uptake and interneuron propagation of tau in vitro, Am. J. Pathol., 187, 1399, 10.1016/j.ajpath.2017.01.022 · DOI · Paper page
  37. Spencer, 2018, Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders, Acta Neuropathol., 136, 69, 10.1007/s00401-018-1869-0 · DOI
  38. Dam, 2021, Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial, Nat. Med., 27, 1451, 10.1038/s41591-021-01455-x · DOI
  39. Höglinger, 2021, Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial, Lancet Neurol., 20, 182, 10.1016/S1474-4422(20)30489-0 · DOI
  40. Jabbari, 2021, Tau-targeting antibody therapies: too late, wrong epitope or wrong target?, Nat. Med., 27, 1341, 10.1038/s41591-021-01465-9 · DOI
  41. Courade, 2018, Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau, Acta Neuropathol., 136, 729, 10.1007/s00401-018-1911-2 · DOI
  42. Arakhamia, 2020, Posttranslational modifications mediate the structural diversity of tauopathy strains, Cell, 180, 633, 10.1016/j.cell.2020.01.027 · DOI
  43. Falcon, 2018, Structures of filaments from Pick's disease reveal a novel tau protein fold, Nature, 561, 137, 10.1038/s41586-018-0454-y · DOI
  44. Falcon, 2019, Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules, Nature, 568, 420, 10.1038/s41586-019-1026-5 · DOI
  45. Sawaya, 2007, Atomic structures of amyloid cross-beta spines reveal varied steric zippers, Nature, 447, 453, 10.1038/nature05695 · DOI
  46. Seidler, 2018, Structure-based inhibitors of tau aggregation, Nat. Chem., 10, 170, 10.1038/nchem.2889 · DOI
  47. Mirbaha, 2018, Inert and seed-competent tau monomers suggest structural origins of aggregation, eLife, 7, e36584, 10.7554/eLife.36584 · DOI
  48. Moreira, 2021, Dynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding, Nat. Commun., 12, 6292, 10.1038/s41467-021-26584-2 · DOI · Paper page
  49. Mok, 2018, Mapping interactions with the chaperone network reveals factors that protect against tau aggregation, Nat. Struct. Mol. Biol., 25, 384, 10.1038/s41594-018-0057-1 · DOI
  50. Carlomagno, 2021, The AD tau core spontaneously self-assembles and recruits full-length tau to filaments, Cell Rep., 34, 108843, 10.1016/j.celrep.2021.108843 · DOI
  51. Zhang, 2019, Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's diseases, eLife, 8, e43584, 10.7554/eLife.43584 · DOI · Paper page
  52. Dutt, 2020, Real-world evidence of caplacizumab use in the management of acute TTP, Blood, 137, 1731, 10.1182/blood.2020007599 · DOI
  53. Matz, 2012, Phage display and selections on purified antigens, Methods Mol. Biol., 907, 213, 10.1007/978-1-61779-974-7_11 · DOI
  54. Danis, 2016, Nuclear magnetic resonance spectroscopy for the identification of multiple phosphorylations of intrinsically disordered proteins, J. Vis. Exp., 10.3791/55001 · DOI
  55. Luna-Vargas, 2011, Enabling high-throughput ligation-independent cloning and protein expression for the family of ubiquitin specific proteases, J. Struct. Biol., 175, 113, 10.1016/j.jsb.2011.03.017 · DOI
  56. Smet, 2004, Accepting its random coil nature allows a partial NMR assignment of the neuronal Tau protein, Chembiochem., 5, 1639, 10.1002/cbic.200400145 · DOI
  57. Lippens, 2004, Proline-directed random-coil chemical shift values as a tool for the NMR assignment of the tau phosphorylation sites, Chembiochem., 5, 73, 10.1002/cbic.200300763 · DOI
  58. Cadwell, 1992, Randomization of genes by PCR mutagenesis, PCR Methods Appl., 2, 28, 10.1101/gr.2.1.28 · DOI
  59. Vojtek, 1995, Ras-Raf interaction: two-hybrid analysis, Methods Enzymol., 255, 331, 10.1016/S0076-6879(95)55036-4 · DOI
  60. Fromont-Racine, 1997, Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens, Nat. Genet., 16, 277, 10.1038/ng0797-277 · DOI
  61. Karlsson, 2006, Analyzing a kinetic titration series using affinity biosensors, Anal. Biochem., 349, 136, 10.1016/j.ab.2005.09.034 · DOI · Paper page
  62. Vagin, 2010, Molecular replacement with MOLREP, Acta Crystallogr. D Biol. Crystallogr., 66, 22, 10.1107/S0907444909042589 · DOI
  63. Murshudov, 2011, REFMAC5 for the refinement of macromolecular crystal structures, Acta Crystallogr. D Biol. Crystallogr., 67, 355, 10.1107/S0907444911001314 · DOI
  64. Emsley, 2010, Features and development of coot, Acta Crystallogr. D Biol. Crystallogr., 66, 486, 10.1107/S0907444910007493 · DOI · Paper page
  65. Krissinel, 2007, Inference of macromolecular assemblies from crystalline state, J. Mol. Biol., 372, 774, 10.1016/j.jmb.2007.05.022 · DOI
  66. Banning, 2010, A flow cytometry-based FRET assay to identify and analyse protein-protein interactions in living cells, PLoS One, 5, e9344, 10.1371/journal.pone.0009344 · DOI
  67. Schindowski, 2006, Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits, Am. J. Pathol., 169, 599, 10.2353/ajpath.2006.060002 · DOI
  68. Leroy, 2007, Early axonopathy preceding neurofibrillary tangles in mutant tau transgenic mice, Am. J. Pathol., 171, 976, 10.2353/ajpath.2007.070345 · DOI · Paper page

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Metadata

Authors
Danis, C., Dupré, E., Zejneli, O., Caillierez, R., Arrial, A., Bégard, S., Mortelecque, J., Eddarkaoui, S., Loyens, A., Cantrelle, F.-X., Hanoulle, X., Rain, J.-C., Colin, M., Buée, L., & Landrieu, I.
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2022-04
Volume
30
Issue
4
Pages
1484-1499
ISSN
1525-0016
DOI
10.1016/j.ymthe.2022.01.009
PMC
PMC9077319
Cited by
76
References
17
Language
en
Licence
Funders
ANR

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.