NEK7 inhibition attenuates Aβ42-induced cognitive impairment by regulating TLR4/NF-κB and the NLRP3 inflammasome in mice

NEK7 is a serine/threonine kinase that regulates cell mitosis and the activation of the nucleotide-binding oligomerization domainlike (NOD-like) receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, and is related to neuro- inflammation and neuronal damage. The purpose of this study was to explore the role and mechanism of NEK7 in cognitive impairment in Alzheimer's disease (AD). BV2 cells, a microglia cell line, was treated with A beta(42). NEK7 expression was measured with reverse transcription-quantitative polymerase chain reaction and Western blotting. An apoptosis kit was used to determine the apoptotic rate. APPswe/PS1dE9 (APP/PS1) transgenic mice were used as an in vivo AD model. The experimental mice were infected with sh-NEK7 lentivirus to downregulate NEK7. The Morris water maze was conducted to explore the effect of NEK7 downregulation on cognitive ability. The results showed that A beta(42) significantly upregulated NEK7 in BV2 cells. Silencing NEK7 suppressed the decrease in BV2 viability and the increase in inflammation, oxidative stress and apoptosis induced by A beta(42). NEK7 mediated it effects through the TLR4/NF-kappa B signalling pathway and the NLRP3 inflammasome. Finally, inhibition of NEK7 alleviated the cognitive impairment in APP/PS1 mice. In conclusion, Silencing NEK7 suppresses A beta(42)-induced cell apoptosis, inflammation and oxidative stress, and improves cognitive performance in AD mice. NEK7 may be a potential target for AD treatment.