Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models-Reference-Cited by-同舟云学术

Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models

Published:2023-03-31 Issue:6639 Volume:379 Page:1336-1341
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Mukadam Aamir S.¹²^ORCID,Miller Lauren V. C.¹²^ORCID,Smith Annabel E.¹²^ORCID,Vaysburd Marina³,Sakya Siri A.⁴⁵^ORCID,Sanford Sophie¹²^ORCID,Keeling Sophie¹²^ORCID,Tuck Benjamin J.¹²^ORCID,Katsinelos Taxiarchis¹²^ORCID,Green Chris¹²^ORCID,Skov Lise¹²^ORCID,Kaalund Sanne S.²^ORCID,Foss Stian⁴⁵^ORCID,Mayes Keith³,O’Connell Kevin³,Wing Mark³,Knox Claire³,Banbury Jessica³,Avezov Edward¹²^ORCID,Rowe James B.²⁶^ORCID,Goedert Michel³^ORCID,Andersen Jan Terje⁴⁵^ORCID,James Leo C.³^ORCID,McEwan William A.¹²^ORCID

Affiliation:

1. UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK.

2. Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK.

3. MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.

4. Department of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, N-0424 Oslo, Norway.

5. Institute of Clinical Medicine and Department of Pharmacology, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway.

6. Cambridge University Hospitals NHS Trust, Cambridge CB2 0SZ, UK.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.abn1366

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