C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer's disease.

ABSTRACT: Multiple studies have recognized the involvement of the complement cascade during Alzheimer's disease pathogenesis. However, the specific role of C5a-C5aR1 signaling in the progression of this neurodegenerative disease is still not clear. Furthermore, its potential as a therapeutic target to treat AD still remains to be elucidated. Canonically, generation of the anaphylatoxin C5a as the result of complement activation and interaction with its receptor C5aR1 triggers a potent inflammatory response. Previously, genetic ablation of C5aR1 in a mouse model of Alzheimer's disease exerted a protective effect by preventing cognitive deficits. Here, using PMX205, a potent, specific C5aR1 antagonist, in the Tg2576 mouse model of Alzheimer's disease we show a striking reduction in dystrophic neurites

SUBMITTER: Gomez-Arboledas A 

PROVIDER: S-EPMC9386996 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature