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Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.
Mukadam, Aamir S; Miller, Lauren V C; Smith, Annabel E; Vaysburd, Marina; Sakya, Siri A; Sanford, Sophie; Keeling, Sophie; Tuck, Benjamin J; Katsinelos, Taxiarchis; Green, Chris; Skov, Lise; Kaalund, Sanne S; Foss, Stian; Mayes, Keith; O'Connell, Kevin; Wing, Mark; Knox, Claire; Banbury, Jessica; Avezov, Edward; Rowe, James B; Goedert, Michel; Andersen, Jan Terje; James, Leo C; McEwan, William A.
Afiliación
  • Mukadam AS; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Miller LVC; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Smith AE; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Vaysburd M; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Sakya SA; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Sanford S; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Keeling S; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • Tuck BJ; Department of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, N-0424 Oslo, Norway.
  • Katsinelos T; Institute of Clinical Medicine and Department of Pharmacology, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway.
  • Green C; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Skov L; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Kaalund SS; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Foss S; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Mayes K; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • O'Connell K; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Wing M; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Knox C; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Banbury J; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Avezov E; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Rowe JB; UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.
  • Goedert M; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • Andersen JT; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.
  • James LC; Department of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, N-0424 Oslo, Norway.
  • McEwan WA; Institute of Clinical Medicine and Department of Pharmacology, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway.
Science ; 379(6639): 1336-1341, 2023 03 31.
Article en En | MEDLINE | ID: mdl-36996217
ABSTRACT
Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology. Tau-Ab complexes were internalized to the cytosol of neurons, which enabled T21 engagement and protection against seeded aggregation. Ab-mediated protection against tau pathology was lost in mice that lacked T21. Thus, the cytosolic compartment provides a site of immunotherapeutic protection, which may help in the design of Ab-based therapies in neurodegenerative disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteínas / Inmunización Pasiva / Proteínas tau / Tauopatías / Ubiquitina-Proteína Ligasas / Proteínas de Motivos Tripartitos / Anticuerpos Monoclonales Límite: Animals Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteínas / Inmunización Pasiva / Proteínas tau / Tauopatías / Ubiquitina-Proteína Ligasas / Proteínas de Motivos Tripartitos / Anticuerpos Monoclonales Límite: Animals Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido