Long noncoding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) is closely implicated in neurological or degenerative diseases, while its implication in AD is rarely reported. This study aimed to investigate the effect of lnc-NEAT1 knockdown on neuron injury, inflammation, and oxidative stress in AD, as well as its interaction with downstream targets and pathways.

APPswe/PS1dE9 transgenic mice were injected with negative control or lnc-NEAT1 interference lentivirus. Besides, AD cellular model was constructed by amyloid β treatment in mice primary neuron cells; then, knockdown of lnc-NEAT1 and microRNA-193a (miR-193a) was performed alone or in combination.

In vivo experiments revealed that Lnc-NEAT1 knockdown improved cognition in AD mice reflected by Morrison water maze and Y-maze assays. Besides, lnc-NEAT1 knockdown reduced injury and apoptosis, decreased TNF-α and IL-1β levels (indicating lower inflammation level), repressed ROS, MDA but promoted ATP and SOD levels (suggesting lower oxidative stress level), and activated CREB/BDNF and NRF2/NQO1 pathways in hippocampi of AD mice. Notably, lnc-NEAT1 down-regulated miR-193a both in vitro and in vivo; also, it acted as a decoy of miR-193a. In vitro experiments showed that lnc-NEAT1 knockdown decreased apoptosis and oxidative stress, improved cell viability, and also activated CREB/BDNF and NRF2/NQO1 pathways in AD cellular model. Meanwhile, miR-193a knockdown showed the opposite effects, which also attenuated lnc-NEAT1 knockdown-mediated reduction in injury, oxidative stress, and activation of CREB/BDNF and NRF2/NQO1 pathways of AD cellular model.

Lnc-NEAT1 knockdown reduces neuron injury, inflammation, and oxidative stress through activating miR-193a mediated CREB/BDNF and NRF2/NQO1 pathways in AD.

No Funding