MicroRNA-455-5p/CPEB1 pathway mediates Aβ-related learning and memory deficits in a mouse model of Alzheimer's disease.

Abstract Alzheimer’s disease (AD), a common neurodegenerative disease, is the main cause of dementia, with cognitive decline as the core symptom observed during diagnosis. Synaptic loss may be the main cause of early cognitive dysfunction in AD, but the detailed mechanism is still unclear. In this study, we investigated the role of abnormal miR-455-5p/CPEB1 pathway in AD mouse model. We found that miR-455-5p was upregulated, while its downstream target, cytoplasmic polyadenylation element-binding 1 (CPEB1), was downregulated in the hippocampus of APP/PS1 mice at the age of 9 m. Abnormal miR-455-5p/CPEB1 pathway mediated cognitive deficits in APP/PS1 mice through suppressing α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor expressions. And miR-455-5p suppression, CPEB1 overexpression or application of a peptide disrupting the miR-455-5p/CPEB1 interaction in CA1 of APP/PS1 mice rescued AD-like phenotypes in mice, including deficits in synaptic plasticity and memory. In conclusion, our results indicated that miRNA-455-5p/CPEB1 pathway mediated synaptic and memory deficits in Alzheimer’s Disease through targeting on AMPARs, providing a potential therapeutic strategy for AD.