PBX1 Improves Cognition and Reduces Amyloid-β Pathology in APP/PS1 Mice by Transcriptionally Activating the CRTC2-CREB Pathway.

ABSTRACT: Alzheimer's disease (AD) is characterized by progressive cognitive decline, amyloid β (Aβ) deposition, and synaptic dysfunction. However, the mechanisms underlying neurodegeneration remain poorly understood. In this study, we investigated the therapeutic potential of PBX1, a transcriptional regulator implicated in neurodevelopment and neuroprotection, against AD. PBX1 expression was significantly downregulated in postmortem hippocampal tissues from patients with AD and in the APP/PS1 mouse model. In vitro, PBX1a knockdown reduced neurite complexity and increased apoptosis. PBX1a overexpression reversed these effects and reduced soluble Aβ_1-40 and Aβ_1-42 levels. In vivo, hippocampal overexpression of PBX1a restored spatial learning and memory, reduced Aβ burden by 41%,

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12741244 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature