MicroRNAs 99b-5p/100-5p Regulated by Endoplasmic Reticulum Stress are Involved in Abeta-Induced Pathologies

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Alzheimer's disease (AD) is a leading cause of dementia, characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles.
• MicroRNAs (miRNAs) are crucial regulators of gene expression with potential as biomarkers in neurodegenerative diseases.
• The roles of specific miRNAs, like miR-99b-5p and miR-100-5p, in Aβ-induced neuronal pathology remain to be fully elucidated.

Purpose of the Study:

• To investigate the expression patterns of miR-99b-5p and miR-100-5p in an Alzheimer's disease mouse model.
• To determine the functional impact of these miRNAs on Aβ-induced neuronal apoptosis.
• To identify the molecular pathways, specifically the mammalian target of rapamycin (mTOR) pathway, involved in the action of miR-99b-5p and miR-100-5p in AD.

Main Methods:

• Analysis of miR-99b-5p and miR-100-5p expression in the brains of APPswe/PS1ΔE9 transgenic mice at various ages compared to wild-type controls.
• In vitro studies using cultured cells treated with Aβ to observe miRNA expression changes and cellular responses.
• Confirmation of mTOR as a direct target of miR-99b-5p and miR-100-5p.

Main Results:

• miR-99b-5p and miR-100-5p expression levels showed dynamic changes in APP/PS1 mice, decreasing in early stages and increasing in later stages of AD pathology.
• Similar expression trends were observed in Aβ-treated cultured neurons.
• miR-99b-5p and miR-100-5p were confirmed to target mTOR and promote Aβ-induced neuronal apoptosis, potentially through the mTOR signaling pathway.

Conclusions:

• miR-99b-5p and miR-100-5p play significant roles in Aβ-induced neuronal apoptosis by targeting the mTOR pathway.
• The dynamic expression of these miRNAs during AD pathogenesis may be linked to endoplasmic reticulum (ER) stress.
• The "ER stress-miRNAs-mTOR" axis represents a potential therapeutic target for Alzheimer's disease.