Potential Regulatory Role of miR-21 on Alzheimer’s Disease by Targeting GSK-3β Signaling

Abstract

Background: Alzheimer’s disease (AD) is the most important neurogenerative disorder with progressive dementia as its main clinical manifestation. The microRNAs (miRNAs) are identified as crucial modulators in AD progression. Nevertheless, the biological potential of miR-21 in AD is obscure. Hence, this study aimed to evaluate the possible role of miR-21 in the pathogenesis of AD via phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK-3β) signaling. Materials and Methods: The miR-21 expression in the brain tissues of patients with AD, as well as normal brain tissues and Aβ1-42-stimulated SH-SY5Y cell line (AD model) was examined by in situ hybridization and quantitative real-time polymerase chain reaction. Also, the apoptosis-linked protein levels as well as programmed cell death 4 (PDCD4) were detected by western blot. Results: Our findings revealed that miR-21 was low expressed in the brain tissues of patients with AD and AD model (P<0.01). Also, the miR-21 overexpression could inhibit apoptosis of the AD model (P<0.01). Indeed, the miR-21 negatively regulated PDCD4 expression, which led to activated PI3K/AKT/GSK-3β signaling. Conclusion: Our study demonstrated that miR-21 cloud inhibits cell apoptosis in AD through the activation of PI3K/AKT/GSK-3β signaling pathway using inhibition of PDCD4 expression.