Open AccessmiR-212-3p attenuates neuroinflammation of rats with Alzheimer's disease via regulating the SP1/BACE1/NLRP3/Caspase-1 signaling pathway
Author(s) -
Weiping g,
Chuanhong Bao,
Yixin Chen,
Wei Zhi-quan
Publication year - 2022
Publication title -
bosnian journal of basic medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 25
eISSN - 1840-4812
pISSN - 1512-8601
DOI - 10.17305/bjbms.2021.6723
Subject(s) - neuroinflammation , pyroptosis , microbiology and biotechnology , neuroprotection , viability assay , signal transduction , morris water navigation task , amyloid precursor protein , caspase 1 , medicine , alzheimer's disease , pharmacology , neuroscience , biology , apoptosis , receptor , inflammasome , immunology , biochemistry , inflammation , disease , hippocampus
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.