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

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.

A role for astrocytic miR-129-5p in Frontotemporal Dementia

“…Reductions in its levels have been associated with memory impairment in mice [34] [35] [36], and miR-212-5p is known to be decreased in several neurodegenerative diseases such as Alzheimer’s disease (AD), Huntington’s disease, and Parkinson’s disease (PD) [37] [38] [39] [40] [41] [42] [43] [44] [45]. Additional studies suggest that targeting miR-212-5p expression is neuroprotective in models of PD, AD, and traumatic brain injury [46] [47] [48]. MiR-212-5p forms a cluster with miR-132 [36], which has also been linked to neurodegenerative diseases.…”

“…Moreover, miR-212-5p was found decreased in several other neurodegenerative diseases such as AD, Huntington’s disease, and PD [37] [38] [39] [40] [41] [42] [43] [44] [45], indicating a key role in neurodegenerative diseases. Additional studies suggest that targeting miR-212-5p expression is neuroprotective in models of PD, AD, and traumatic brain injury [46] [47] [48].…”

Sevoflurane Postconditioning Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting SP1/ACSL4-Mediated Ferroptosis

“…In addition, SP1 is upregulated in neuropathological developments, including PD and Alzheimer's disease. 40,41 Furthermore, Qin et al 42 showed that inhibition of SP1 activation effectively inhibits OGD/ R-induced microglial inflammatory activation. Recent evidence suggests that SP1 expression is increased in ischemic/ hypoxic conditions.…”

Non-coding RNAs: The Neuroinflammatory Regulators in Neurodegenerative Diseases

“…lncRNA-SNHG14 was found to down-regulate miR-223-3p and then up-regulate NLRP3 expression in the AD study (68). While miR-212 attenuated neuroinflammation in AD rats by inhibiting SP1 expression to block BACE1-induced NLRP3 activation (69).…”