Protein degradation impairment and synapse elimination by microglia in BSN P3866A knock‐in mouse model of tauopathy
Our BSNKI mouse model, reflecting a disease-associated BSN mutation, revealed motor impairments and pathological tau and BSN deposits, mirroring observations in BSN mutation carriers. Notably, BSN seems to play a dual role, promoting tau aggregation and sequestering protein degradation molecules, leading to tau and protein accumulation at the soma and synapse, triggering microgliosis and neuroinflammation. These findings propose BSN as a promising therapeutic target for tauopathies, underscoring the need for further exploration to elucidate underlying mechanisms and therapeutic implications.
Authors
- Nur Jury (ORCID: https://orcid.org/0000-0002-1143-3595)
- Pablo Martínez (ORCID: https://orcid.org/0000-0003-3496-4652)
- Ichiro Yabe (ORCID: https://orcid.org/0000-0002-1734-7997)
- Yanwen You
- Naomi Kouri (ORCID: https://orcid.org/0000-0002-6841-9882)
- Cristian A Lasagna Reeves
- Melissa E. Murray (ORCID: https://orcid.org/0000-0001-7379-2545)
- Hiroaki Yaguchi (ORCID: https://orcid.org/0000-0001-6643-8740)
- Henika Patel (ORCID: https://orcid.org/0000-0002-2654-4669)
- Shinya Tanaka (ORCID: https://orcid.org/0000-0001-6470-3301)
- Darren M. Rothberg
- Koichi Wakabayashi (ORCID: https://orcid.org/0000-0002-3756-7209)
- Daniella Lopes
- Katie Vanderbosch
Institutions
- Hirosaki University (JP)
- Hokkaido University (JP)
- WinnMed (US)
- Mayo Clinic in Florida (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.090096
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00