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 through regulating the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)/Caspase-1 signaling pathway. The AD rat model was established through 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 through 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.
Highlights
Alzheimer’s disease (AD), the major subtype of dementia, is known as a progressive neurodegenerative disease in the elder [1]
To explore the functional mechanism of miR-212-3p in AD, the AD rat model was established using the treatment of Amyloid-β 1-42 (Aβ1-42), followed by injection of miR-212-3p agomir
Upon miR212-3p overexpression, escape latency was markedly shortened, while time in the target quadrant and time to pass the target area were markedly prolonged (P
Summary
Alzheimer’s disease (AD), the major subtype of dementia, is known as a progressive neurodegenerative disease in the elder [1]. Neuroinflammation process in AD, which is a response to the generation of Aβ, hyperphosphorylated tau protein and oxidative molecules, is important to be resolved in order to alleviate the symptoms of the disease [6, 7]. Only a few molecules targeting neuroinflammation displayed effects convincing enough to support their usage in clinical treatment [5]. In this context, the discovery of novel molecules with conclusive efficacy in neuroinflammation may confer a glimmer of hope for the AD management
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