Deregulated lncRNA MAGI2-AS3 in Alzheimer's disease attenuates amyloid-β induced neurotoxicity and neuroinflammation by sponging miR-374b-5p.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is a common neurodegenerative disease, which is characterized by aberrant accumulation of amyloid-β (Aβ) and neuroinflammation. The purpose of this study was to explore the regulatory effects of long non-coding RNA (lncRNA) MAGI2-AS3 and microRNA-374b-5p (miR-374b-5p) on Aβ-induced neurotoxicity and neuroinflammation, as well as the relationship between MAGI2-AS3 and miR-374b-5p in AD patients.

METHODS:

A luciferase reporter assay was used to analyze the interaction between MAGI2-AS3 and miR-374b-5p and between miR-374b-5p and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). SH-SY5Y and BV2 cells treated with Aβ25-35 were used to mimic neuronal injury and neuroinflammation in AD pathogenesis. Cell viability was evaluated using a MTT assay, and pro-inflammatory cytokine levels were measured using ELISA kits. MAGI2-AS3 and miR-374b-5p expression was examined using quantitative real-time PCR.

RESULTS:

BACE1 served as a target gene of miR-374b-5p, and MAGI2-AS3 could sponge miR-374b-5p. The expression of MAGI2-AS3 was increased, and miR-374b-5p was decreased in both SH-SY5Y and BV2 cells exposed to Aβ25-35. MAGI2-AS3 reduction enhanced neuronal viability and attenuated neuroinflammation in AD cell models, and miR-374b-5p overexpression led to same effects, but miR-374b-5p inhibition reversed these effects. Serum MAGI2-AS3 and miR-374b-5p levels in AD patients were negatively correlated and correlated with disease severity.

CONCLUSION:

The findings indicated that the MAGI2-AS3/miR-374b-5p axis regulates Aβ-induced neurotoxicity in SH-SY5Y cells and neuroinflammation in BV2 cells. The MAGI2-AS3/miR-374b-5p axis may provide novel biomarkers and therapeutic targets for AD.

• Authors: Jingjing Zhang, Rui Wang
• Journal: Experimental gerontology (Exp Gerontol) Vol. 144 Pg. 111180 (02 2021) ISSN: 1873-6815 [Electronic] England
• PMID: 33279663 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• MicroRNAs
• RNA, Long Noncoding
• Guanylate Kinases
• MAGI2 protein, human
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases

Topics

• Adaptor Proteins, Signal Transducing
• Alzheimer Disease (genetics)
• Amyloid Precursor Protein Secretases (genetics)
• Aspartic Acid Endopeptidases (genetics)
• Cell Line, Tumor
• Guanylate Kinases
• Humans
• MicroRNAs (genetics)
• Neurodegenerative Diseases
• RNA, Long Noncoding (genetics)