title: Reelin Expression in Creutzfeldt-Jakob Disease and Experimental Models of Transmissible Spongiform Encephalopathies.
abstract: Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule, in turn mediated by binding Reelin to its receptors. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in Alzheimer's disease. However, putative changes in Reelin are not described in natural prionopathies or experimental models of prion infection or toxicity. With this is mind, in the present study, we determined that Reelin protein and mRNA levels increased in CJD human samples and in mouse models of human prion disease in contrast to murine models of prion infection. However, changes in Reelin expression appeared only at late terminal stages of the disease, which prevent their use as an efficient diagnostic biomarker. In addition, increased Reelin in CJD and in in vitro models does not correlate with Dab1 phosphorylation, indicating failure in its intracellular signaling. Overall, these findings widen our understanding of the putative changes of Reelin in neurodegeneration.
authors.affiliation: Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-21, 08028, Barcelona, Spain.|Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Agata
authors.initials: A
authors.lastname: Mata
authors.affiliation: Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-21, 08028, Barcelona, Spain.|Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Urrea
authors.affiliation: Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-21, 08028, Barcelona, Spain.|Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vilches
authors.affiliation: Department of Neurology, German Center for Neurodegenerative Diseases - DZNE, Universitätsmedizin Göttingen, Bonn, Germany.
authors.forename: Franc
authors.initials: F
authors.lastname: Llorens
authors.affiliation: Department of Neurology, German Center for Neurodegenerative Diseases - DZNE, Universitätsmedizin Göttingen, Bonn, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Thüne
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Valdeolmos, Spain.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.affiliation: UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782, Santiago de Compostela, Spain.|Department of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Sevillano
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Valdeolmos, Spain.
authors.forename: Juan María
authors.initials: JM
authors.lastname: Torres
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782, Santiago de Compostela, Spain.|Department of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
authors.forename: Jesús Rodríguez
authors.initials: JR
authors.lastname: Requena
authors.affiliation: Department of Neurology, German Center for Neurodegenerative Diseases - DZNE, Universitätsmedizin Göttingen, Bonn, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.affiliation: Institut de Neuropatologia, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-21, 08028, Barcelona, Spain.|Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Rosalina
authors.initials: R
authors.lastname: Gavín
authors.affiliation: Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-21, 08028, Barcelona, Spain. jadelrio@ibecbarcelona.eu.|Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain. jadelrio@ibecbarcelona.eu.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. jadelrio@ibecbarcelona.eu.|Institute of Neuroscience, University of Barcelona, Barcelona, Spain. jadelrio@ibecbarcelona.eu.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Del Río
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Cellular prion protein; Creutzfeldt-Jakob disease; Dab-1; Reelin