The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex
Cheng-Niu Wang1, Ying-Jie Wang, Hao Wang
1Basic Medical Research Centre, Medical College, Nantong University.
Abstract:
Alzheimer's disease (AD) is a most serious age-related neurodegenerative disorder accompanied with significant memory impairments in this world. Recently, microRNAs (miRNAs) have been reported to be invlolved in the pathophysiology of AD. Previous studies have shown that miRNA-206 (miR-206) is implicated in the pathogenesis of AD via suppressing the expression of brain-derived neurotrophic factor (BDNF) in the brain. Here, we examined the miR-206-3p and miR-206-5p expression in the hippocampus and cortex of Abeta precursor protein (APP)/presenilin-1 (PS1) transgenic mice treated with donepezil, a drug approved for treating AD in clinic. We found that the expression of miR-206-3p was significantly up-regulated in the hippocampus and cortex of APP/PS1 mice, while donepezil administration significantly reversed this dysfunction. In addition, enhancing the miR-206-3p level by the usage of AgomiR-206-3p significantly attenuated the anti-dementia effects of donepezil in APP/PS1 mice. Together, these results suggested that miR-206-3p is involved in the anti-dementia effects of donepezil, and could be a novel pharmacological target for treating AD.
Insights
Alzheimer's disease involves altered microRNA-206-3p levels. Donepezil treatment reversed this in mice, suggesting miR-206-3p is a potential therapeutic target for Alzheimer's disease treatments.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of age-related neurodegeneration and memory loss.
- MicroRNAs (miRNAs) are increasingly recognized for their role in AD pathogenesis.
- Brain-derived neurotrophic factor (BDNF) suppression by microRNA-206 (miR-206) is implicated in AD.
Purpose of the Study:
- To investigate the expression of miR-206-3p and miR-206-5p in an Alzheimer's disease mouse model.
- To determine the effect of donepezil, an approved AD drug, on miR-206-3p levels.
- To explore the role of miR-206-3p in the therapeutic mechanisms of donepezil.
Main Methods:
- Utilized Abeta precursor protein (APP)/presenilin-1 (PS1) transgenic mice, a model for Alzheimer's disease.
- Analyzed miR-206-3p and miR-206-5p expression in hippocampal and cortical tissues.
- Administered donepezil and an AgomiR-206-3p agent to assess therapeutic effects and molecular interactions.
Main Results:
- miR-206-3p expression was significantly upregulated in the hippocampus and cortex of APP/PS1 mice.
- Donepezil treatment normalized the elevated miR-206-3p levels in these mice.
- Enhancing miR-206-3p levels with AgomiR-206-3p diminished the anti-dementia effects of donepezil.
Conclusions:
- miR-206-3p is implicated in the pathophysiology of Alzheimer's disease.
- The anti-dementia effects of donepezil are associated with modulation of miR-206-3p.
- miR-206-3p represents a potential novel pharmacological target for Alzheimer's disease therapy.
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