Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils
Our findings identify GPR34 as a promising therapeutic target for enhancing microglial Aβ clearance and highlight the potential of GPR34 agonists for AD treatment. The age-dependent decline in GPR34 expression may contribute to reduced Aβ clearance efficiency in aging brains, exacerbating amyloid accumulation. Pharmacological activation of GPR34 represents a novel strategy to counteract impaired Aβ clearance in both aging and AD brains, potentially modifying disease progression through enhancement of microglial phagocytic function.
Authors
- Norikazu Hara (ORCID: https://orcid.org/0000-0001-8525-3469)
- Tomohiko Ohwada (ORCID: https://orcid.org/0000-0001-5390-0203)
- Takaomi C. Saido (ORCID: https://orcid.org/0000-0003-1970-6903)
- Shigeo Murayama (ORCID: https://orcid.org/0000-0001-9709-5242)
- Junken Aoki (ORCID: https://orcid.org/0000-0001-9435-1896)
- Sho Takatori (ORCID: https://orcid.org/0000-0002-3925-4011)
- Hideyuki Okano (ORCID: https://orcid.org/0000-0001-7482-5935)
- Iki Sonn
- Takeshi Ikeuchi
- M. Hasegawa (ORCID: https://orcid.org/0000-0001-9234-6014)
- Maho Morishima
- Takashi Saito (ORCID: https://orcid.org/0000-0001-9495-3547)
- Toshiyuki Takai (ORCID: https://orcid.org/0000-0002-4549-7116)
- Jumpei Omi (ORCID: https://orcid.org/0000-0003-2503-6045)
- Hayato Etani
- Masataka Kikuchi (ORCID: https://orcid.org/0000-0002-9562-841X)
- Yusuke Amiya
- Taisuke Tomita (ORCID: https://orcid.org/0000-0002-0075-5943)
- Akinori Miyashita (ORCID: https://orcid.org/0000-0003-2508-9649)
- Aika Akahori
- Wenbo Wang (ORCID: https://orcid.org/0000-0001-5501-1039)
- H Watanabe (ORCID: https://orcid.org/0000-0003-4963-260X)
- Yuko Saito (ORCID: https://orcid.org/0000-0002-9974-8638)
Institutions
- Tohoku University (JP)
- Keio University (JP)
- RIKEN Center for Brain Science (JP)
- Nagoya City University (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Niigata University (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Alzheimer s Research & Therapy
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1186/s13195-025-01891-8
- Citations
- 3
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.49
Funders
- Japan Society for the Promotion of Science