PMID- 37286157 OWN - NLM STAT- MEDLINE DCOM- 20231010 LR - 20231011 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 529 DP - 2023 Oct 1 TI - Targeting lncRNA NEAT1 Hampers Alzheimer's Disease Progression. PG - 88-98 LID - S0306-4522(23)00103-3 [pii] LID - 10.1016/j.neuroscience.2023.02.016 [doi] AB - 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 beta 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. CI - Copyright (c) 2023. Published by Elsevier Ltd. FAU - Li, Yuanlong AU - Li Y AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Fan, Hua AU - Fan H AD - School of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Henan University of Science and Technology, Luoyang, Henan, China. FAU - Ni, Ming AU - Ni M AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Clinical Pharmacy, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China. FAU - Zhang, Wei AU - Zhang W AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Fang, Fengqin AU - Fang F AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Sun, Jun AU - Sun J AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Lyu, Pin AU - Lyu P AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Ma, Peizhi AU - Ma P AD - Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. Electronic address: mpeizhi@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230605 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Amyloid beta-Peptides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MicroRNAs) RN - 0 (NF-E2-Related Factor 2) RN - 0 (RNA, Long Noncoding) RN - 0 (NEAT1 long non-coding RNA, mouse) SB - IM MH - Animals MH - Mice MH - *Alzheimer Disease/genetics MH - Amyloid beta-Peptides MH - Apoptosis/genetics MH - Brain-Derived Neurotrophic Factor MH - Inflammation/metabolism MH - *MicroRNAs/genetics/metabolism MH - NF-E2-Related Factor 2/genetics MH - *RNA, Long Noncoding/genetics/metabolism OTO - NOTNLM OT - Alzheimer's disease OT - Lnc-NEAT1 OT - cognitive impairment OT - neuron injury OT - oxidative stress EDAT- 2023/06/08 01:08 MHDA- 2023/10/09 06:41 CRDT- 2023/06/07 19:28 PHST- 2022/10/19 00:00 [received] PHST- 2023/02/13 00:00 [revised] PHST- 2023/02/20 00:00 [accepted] PHST- 2023/10/09 06:41 [medline] PHST- 2023/06/08 01:08 [pubmed] PHST- 2023/06/07 19:28 [entrez] AID - S0306-4522(23)00103-3 [pii] AID - 10.1016/j.neuroscience.2023.02.016 [doi] PST - ppublish SO - Neuroscience. 2023 Oct 1;529:88-98. doi: 10.1016/j.neuroscience.2023.02.016. Epub 2023 Jun 5.