MiR-9-5p inhibits mitochondrial damage and oxidative stress in AD cell models by targeting GSK-3β

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation.
• MicroRNAs (miRNAs) play critical roles in regulating gene expression and are implicated in AD pathogenesis.
• MicroRNA-9-5p (miR-9-5p) has emerged as a potential regulator in neurological conditions.

Purpose of the Study:

• To investigate the effects of miR-9-5p overexpression on Aβ-induced neuronal damage in a mouse hippocampal cell line (HT22).
• To elucidate the underlying molecular mechanisms, including the role of glycogen synthase kinase-3β (GSK-3β) and Nrf2/Keap1 signaling pathway.

Main Methods:

• Establishment of an AD cell model using Aβ25-35 treatment in HT22 cells.
• Assessment of cell viability using CCK-8 assay.
• Quantification of miR-9-5p and GSK-3β mRNA levels via RT-qPCR.
• Analysis of HT22 cell apoptosis using flow cytometry.
• Investigation of Nrf2/Keap1 signaling pathway activation.

Main Results:

• Aβ25-35 treatment significantly downregulated miR-9-5p expression in HT22 cells.
• Overexpression of miR-9-5p inhibited Aβ25-35-induced mitochondrial dysfunction, apoptosis, and oxidative stress.
• miR-9-5p directly targeted and regulated GSK-3β expression.
• miR-9-5p overexpression, by targeting GSK-3β, activated the Nrf2/Keap1 pathway, increasing Nrf2, HO-1, SOD-1, and GCLC, and decreasing Keap1.

Conclusions:

• miR-9-5p plays a protective role in Aβ-induced neurotoxicity.
• The protective effects of miR-9-5p involve the regulation of GSK-3β and the subsequent activation of the Nrf2/Keap1 antioxidant pathway.
• miR-9-5p represents a potential therapeutic target for Alzheimer's disease.