Ablation of progranulin augments microglial activation and accelerates prion progression.

ABSTRACT: Mutations or polymorphisms in GRN, encoding the CNS glycoprotein progranulin (PGRN), have been linked to several neurodegenerative diseases. In this study, we explored the role of PGRN in prion diseases. We observed that prion infection upregulated microglial PGRN expression. Following intracerebral inoculation with RML6 prions, Grn^-/- mice exhibited accelerated disease progression compared to Grn^+/- and Grn^+/+ littermates. Histological analysis revealed augmented microglial activation in Grn^-/- mice. Temporal analysis revealed enhanced early microglial activation and prion clearance at 120 dpi, followed by excessive complement activation but inadequate clearance by 150 dpi. Additionally, Grn^-/- brains exhibited exacerbated astrogliosi

SUBMITTER: Li B 

PROVIDER: S-EPMC12519607 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature