LINC00472 regulates ferroptosis of neurons in Alzheimer's disease via FOXO 1.

Abstract

OBJECTIVE To explore the molecular mechanism of long non-coding RNA (lncRNA) LINC00472 in Alzheimer's Disease (AD). METHOD Ferroptosis-related lncRNAs were screened by GEO database. AD mouse model was constructed for in vivo experimental. The content of Aβ protein and Tau protein hyperphosphorylation were examined in Hippocampal tissue samples of mice. Subsequently, HT22 cells were induced with Aβ25-35 to establish a neuronal injury model of AD in vitro. The expression of FOXO1, a key gene for ferroptosis, was verified by overexpressing/knocking down the LINC00472. The effects of LINC00472 on ROS and lipid peroxidation content, GPX4, and Tau protein in AD model cells were examined by ROS assay, MDA assay, Western Blot and qRT-PCR. Subsequently, the expression of iron ion, FTH, TfRC, and Fpn protein were detected in AD cells. RESULTS The level of FOXO1 was positively correlated with the degree of AD. In vivo experiments showed that the expression of Aβ and Tau hyperphosphorylated were significantly reduced in the inhibitor group and iron was significantly reduced relative to the AD group. In the AD cell model, the content of lipid peroxide was up-regulated, GPX4 protein and mRNA were decreased, and phosphorylation of Tau protein was enhanced in the AD cell model relative to the control group. Whereas knocking down LINC00472 inhibited the up-regulation of lipid peroxide, decreased the level of GPX4, and enhancement of Tau protein phosphorylation, and it reduced iron accumulation, in AD cells. CONCLUSIONS LINC00472 affects ferroptosis in AD by regulating iron accumulation, in neuronal cells.