Tau monoclonal antibody generation based on humanized yeast models
| Autor: | Rosseels, Joëlle, van den Brande, Jeff, Violet, Marie-Luce, Jacobs, Dirk, Grognet, Pierre, Lopez, Juan, Huvent, Isabelle, Caldara, Marina, Swinnen, Erwin, Papegaey, Anthony, Caillierez, Raphaelle, Buée-Scherrer, Valerie, Engelborghs, Sebastiaan, Lippens, Guy, Colin, Morvane, Buée, Luc, Galas, Marie-Christine, Vanmechelen, Eugeen, Winderickx, Joris |
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| Přispěvatelé: | Vesalius College, Department of Bio-engineering Sciences, Pathologic Biochemistry and Physiology, Clinical sciences, Neurology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Antwerp (UA), ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), CHU Lille, CNRS, Université de Lille, Inserm, Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], University of Antwerp [UA], Lille Neurosciences & Cognition (LilNCog) - U 1172, Université de Lille, LillOA, Laboratoires d'excellence - Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime - - DISTALZ2011 - ANR-11-LABX-0009 - LABX - VALID, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Peptide Fragments/metabolism
Protein Folding [SDV.BIO]Life Sciences [q-bio]/Biotechnology mice [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Blotting Western tau Proteins Enzyme-Linked Immunosorbent Assay Mice Transgenic Plaque Amyloid Saccharomyces cerevisiae Hippocampus Alzheimer Disease/cerebrospinal fluid Immunoenzyme Techniques Membrane Microdomains Neurobiology Alzheimer Disease mental disorders Protein Oligomer Animals Humans Immunoprecipitation Disease Biotinylation Biology Antibody Tau Protein (Tau) Yeast Medicine(all) Mice Inbred BALB C phosphorylation [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Brain Antibodies Monoclonal tau Proteins/cerebrospinal fluid Neurofibrillary Tangles magnetic resonance spectroscopy Peptide Fragments [SDV.BIO] Life Sciences [q-bio]/Biotechnology Chemistry epitope mapping Hippocampus/immunology Disease Progression Immunization Human medicine Brain/immunology |
| Zdroj: | Journal of biological chemistry Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2015, 290 (7), pp.4059-4074. ⟨10.1074/jbc.M114.627919⟩ Journal of Biological Chemistry, 2015, 290 (7), pp.4059-4074. ⟨10.1074/jbc.M114.627919⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, whereas the second, ADx215, detects an epitope formed by the Tau N terminus when Tau is not phosphorylated at Tyr(18). For the third antibody, ADx210, the binding site could not be determined because its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients, and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low order Tau oligomers in diseased brain, which in size correspond to Tau dimers. ADx201 and ADx210 additionally reacted to higher order Tau oligomers and presumed prefibrillar structures in the patient samples. Our data further suggest that formation of the low order Tau oligomers marks an early disease stage that is initiated by Tau phosphorylation at N-terminal sites. Formation of higher order oligomers appears to require additional phosphorylation in the C terminus of Tau. When used to assess Tau levels in human cerebrospinal fluid, the antibodies permitted us to discriminate patients with Alzheimer disease or other dementia like vascular dementia, indicative that these antibodies hold promising diagnostic potential. ispartof: JOURNAL OF BIOLOGICAL CHEMISTRY vol:290 issue:7 pages:4059-4074 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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