Resveratrol alleviates amyloid β‐induced neuronal apoptosis, inflammation, and oxidative and endoplasmic reticulum stress by circ_0050263/miR‐361‐3p/PDE4A axis during Alzheimer's disease

Abstract Resveratrol (Res) has been identified to reduce neurodegeneration. Circular RNAs (circRNAs) are stable noncoding RNAs that are considered to be ideal biomarkers for molecular targeting treatment. Here, this study focused on investigating the function and relationship of circ_0050263 and Res in Alzheimer's Disease (AD). Human neuroblastoma cell line SK‐N‐SH was exposed to amyloid‐β (Aβ) to induce AD cell model in vitro. Cell viability, apoptosis, and inflammatory reaction were evaluated by CCK‐8 assay, flow cytometery, and ELISA analysis. The oxidative stress and endoplasmic reticulum stress (ERS) were determined by detecting related markers. Levels of genes and proteins were detected by qRT‐PCR and Western blot. Dual‐luciferase reporter assay was adopted to verify the binding between miR‐361‐3p and circ_0050263 or PDE4A (Phosphodiesterase 4A). Subsequently, we found that Res treatment alleviated Aβ‐induced apoptosis, inflammatory response, oxidative stress, and ERS in SK‐N‐SH cells. Circ_0050263 is a stable circRNA, which was increased by Aβ, but decreased by Res in SK‐N‐SH cells. Circ_0050263 overexpression reversed Res‐induced neuroprotective effects. Mechanistically, circ_0050263 acted as a sponge for miR‐361‐3p, which targeted PDE4A. Circ_0050263 silencing abated Aβ‐induced neuronal injury, which were counteracted by following PDE4A overexpression. Moreover, PDE4A upregulation could attenuate Res‐mediated neuroprotective effects. In all, Res alleviated Aβ‐induced neuronal apoptosis, inflammation, oxidative stress, and ERS via circ_0050263/miR‐361‐3p/PDE4A axis, providing new insights for AD therapy.