Peptide aptamer targeting Aβ-PrP-Fyn axis reduces Alzheimer's disease pathologies in 5XFAD transgenic mouse model.

ABSTRACT: Currently, no effective therapeutics exist for the treatment of incurable neurodegenerative diseases such as Alzheimer's disease (AD). The cellular prion protein (PrP^C) acts as a high-affinity receptor for amyloid beta oligomers (AβO), a main neurotoxic species mediating AD pathology. The interaction of AβO with PrP^C subsequently activates Fyn tyrosine kinase and neuroinflammation. Herein, we used our previously developed peptide aptamer 8 (PA8) binding to PrP^C as a therapeutic to target the AβO-PrP-Fyn axis and prevent its associated pathologies. Our in vitro results indicated that PA8 prevents the binding of AβO with PrP^C and reduces AβO-induced neurotoxicity in mouse neuroblastoma N2a cells and primary hippocampal neurons. Next, we performed i

SUBMITTER: Ali T 

PROVIDER: S-EPMC10164677 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature