Post-transcriptional regulation of α7 nAChR expression by miR-98-5p modulates cognition and neuroinflammation in an animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a complicated neurodegenerative disease and therefore addressing multiple targets simultaneously has been believed as a promising therapeutic strategy against AD. α7 nicotinic acetylcholine receptor (nAChR), which plays an important role in improving cognitive function and alleviating neuroinflammation in central nervous system (CNS), has been regarded as a potential target in the treatment of AD. However, the regulation of α7 nAChR at post-transcriptional level in mammalian brain remains largely speculated. Herein, we uncovered a novel post-transcriptional regulatory mechanism of α7 nAChR expression in AD and further demonstrated that miR-98-5p suppressed α7 nAChR expression through directly binding to the 3'UTR of mRNA. Knockdown of miR-98-5p activated Ca2+ signaling pathway and consequently reversed cognitive deficits and Aβ burden in APP/PS1 mice. Furthermore, miR-98-5p downregulation increased α7 nAChR expression, and ameliorated neuroinflammation via inhibiting NF-κB pathway and upregulating Nrf2 target genes. Our findings illustrate a prominent regulatory role of miR-98-5p in targeting inflammation and cognition, and provide an insight into the potential of miR-98-5p/α7 nAChR axis as a novel therapeutic strategy for AD.