miR-212-3p attenuates neuroinflammation of rats with Alzheimer's disease via regulating the SP1/BACE1/NLRP3/Caspase-1 signaling pathway

Authors

  • Wei Nong Guangxi University of Chinese Medicine, Nanning, Guangxi, P.R. China
  • Chuanhong Bao Guangxi University of Chinese Medicine, Nanning, Guangxi, P.R. China
  • Yixin Chen Guangxi University of Chinese Medicine, Nanning, Guangxi, P.R. China
  • Zhiquan Wei Guangxi University of Chinese Medicine, Nanning, Guangxi, P.R. China https://orcid.org/0000-0002-7077-0153

DOI:

https://doi.org/10.17305/bjbms.2021.6723

Keywords:

Alzheimer's disease, miR-212-3p, SP1, BACE1, NLRP3/Caspase-1 signaling pathway, Pyroptosis, Transcription factor, Neuroinflammation, Aβ1-42; Pathological injury

Abstract

Alzheimer's disease (AD) ranks as the leading cause of dementia. MicroRNA (miR)-212-3p has been identified to exert neuroprotective effects on brain disorders. The current study analyzed the protective role of miR-212-3p in AD rats via regulating the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/Caspase-1 signaling pathway. The AD rat model was established via injection of amyloid-β 1-42 (Aβ1-42), followed by the Morris water maze test. The morphology and functions of neurons were observed. Furthermore, miR-212-3p, NLRP3, cleaved Caspase-1, gasdermin D N-terminus, interleukin (IL)-1β and IL-18 expressions were measured. H19-7 cells were treated with Aβ1-42 to establish the AD cell model, followed by an assessment of cell viability and pyroptosis. Downstream targets of miR-212-3p and specificity protein 1 (SP1), as well as beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) were predicted by databases and testified using dual-luciferase and chromatin immunoprecipitation assays. miR-212-3p was weakly expressed in AD rats. miR-212-3p overexpression was linked to improved learning and memory capacities of AD rats and reduced neuronal pyroptosis linked to neuroinflammation attenuation. In vitro, miR-212-3p improved viability and suppressed pyroptosis of neurons via inhibiting NLRP3/Caspase-1. Overall, miR-212-3p inhibited SP1 expression to block BACE1-induced activation of NLRP3/Caspase-1, thereby attenuating neuroinflammation of AD rats.

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miR-212-3p attenuates neuroinflammation of rats with Alzheimer's disease via regulating the SP1/BACE1/NLRP3/Caspase-1 signaling pathway

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Published

2022-02-12

How to Cite

1.
Nong W, Bao C, Chen Y, Wei Z. miR-212-3p attenuates neuroinflammation of rats with Alzheimer’s disease via regulating the SP1/BACE1/NLRP3/Caspase-1 signaling pathway. Bosn J of Basic Med Sci [Internet]. 2022Feb.12 [cited 2022May24];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/6723

Issue

Section

Molecular Biology