Targeting lncRNA NEAT1 Hampers Alzheimer's Disease Progression

by Selleckchem | Feb 10 2024

Long noncoding RNA nuclear enriched abundant transcript 1 (lnc-NEAT1) is closely implicated in neurological diseases, while its implication in Alzheimer's disease (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 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 inflammatory cytokine levels, repressed oxidative stress level, and activated adenosine cyclophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (NRF2)/nicotinamide adenine dinucleotide phosphate dehydrogenase 1 (NQO1) pathways in hippocampi of AD mice. Notably, lnc-NEAT1 down-regulated microRNA-193a both in vitro and in vivo and acted as a decoy of microRNA-193a. In vitro experiments showed that lnc-NEAT1 knockdown decreased apoptosis and oxidative stress, improved cell viability, also activated CREB/BDNF and NRF2/NQO1 pathways in AD cellular model. Meanwhile, microRNA-193a knockdown showed the opposite effects, which also attenuated lnc-NEAT1 knockdown-mediated reduction in injury, oxidative stress, and CREB/BDNF and NRF2/NQO1 pathways of AD cellular model. In conclusion, lnc-NEAT1 knockdown reduces neuron injury, inflammation, and oxidative stress through activating microRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways in AD.

Comments:

That's quite a detailed study! It seems like the research explored the impact of reducing lnc-NEAT1 on Alzheimer's disease (AD) progression in both mouse models and cell cultures. The key findings suggest that knocking down lnc-NEAT1:

1. Improved cognition in AD mice, as seen in maze assays.
2. Reduced neuronal injury, apoptosis, inflammatory cytokine levels, and oxidative stress in the hippocampi of AD mice.
3. Activated specific pathways involved in neuronal protection (CREB/BDNF and NRF2/NQO1 pathways).
4. Down-regulated microRNA-193a, acting as a decoy for this molecule.
5. Decreased apoptosis and oxidative stress, improved cell viability, and activated protective pathways in the AD cellular model.

Moreover, the study highlighted an interaction between lnc-NEAT1 and microRNA-193a, suggesting that the beneficial effects of lnc-NEAT1 knockdown might, in part, be mediated through regulating this microRNA.

This research presents promising insights into the potential role of lnc-NEAT1 in mitigating neuronal damage and inflammation in the context of AD. If this can be replicated and further understood in human models, it could pave the way for novel therapeutic approaches targeting lnc-NEAT1 or its associated pathways in AD treatment.

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