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MicroRNA-101a Regulates Autophagy Phenomenon via the MAPK Pathway to Modulate Alzheimer's-Associated Pathogenesis
Qian Li1,2, Yu Wang3,2, Wenjie Peng4
11 Department of Pediatrics, Daping Hospital, Army Medical University, Chongqing, China.
Abstract:
Alzheimer's disease (AD) is a type of neurodegenerative disorder and the most common form of dementia. MicroRNA (miRNA) has been shown to play a role in various diseases, including AD. It also has been reported to regulate autophagy. We extracted miRNA from blood samples and constructed an miRNA-101a lentivirus vector. In this study we found the level of miRNA-101a was significantly reduced in the plasma of patients with AD and APPswe/PS1ΔE9 transgenic mice. The relative expression of miRNA-101a exhibited a relatively high diagnostic performance (area under receiver operating characteristic curve: 0.8725) in the prediction of AD with a sensitivity of 0.913 and a specificity of 0.733 at the threshold of 0.6463. Under electron microscopy, autophagic vacuoles in AD-related cells numbered more than the cells up-regulating miRNA-101a in the in vitro experiments. Dual-luciferase reporter assay and Western blot results proved that the MAPK1 pathway plays a role in the formation of autophagic vacuoles in AD. This study found that the autophagy phenomenon regulated by miRNA-101a via the MAPK pathway might be a new mechanism in AD. This could provide new insights into AD formation and treatment.
Insights
Reduced miRNA-101a levels in Alzheimer's disease (AD) patients correlate with impaired autophagy via the MAPK pathway. This discovery offers new insights into AD mechanisms and potential therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is the most common neurodegenerative dementia.
- MicroRNAs (miRNAs) are implicated in various diseases, including AD, and regulate cellular processes like autophagy.
- Dysfunctional autophagy is increasingly recognized as a factor in AD pathogenesis.
Purpose of the Study:
- To investigate the role of miRNA-101a in Alzheimer's disease.
- To explore the relationship between miRNA-101a, autophagy, and the MAPK pathway in AD.
- To assess the diagnostic potential of miRNA-101a in AD prediction.
Main Methods:
- Extraction of miRNA from blood samples of AD patients and control subjects.
- Construction of an miRNA-101a lentivirus vector for in vitro experiments.
- Analysis of autophagic vacuoles using electron microscopy.
- Dual-luciferase reporter assay and Western blot to investigate pathway involvement.
Main Results:
- Significantly reduced levels of miRNA-101a were observed in the plasma of AD patients and in a mouse model of AD.
- miRNA-101a demonstrated high diagnostic performance for AD prediction (AUC: 0.8725, sensitivity: 0.913, specificity: 0.733).
- In vitro studies showed increased autophagic vacuoles in AD-related cells, with upregulation of miRNA-101a correlating with fewer vacuoles; the MAPK1 pathway was implicated.
Conclusions:
- A significant reduction in plasma miRNA-101a is a hallmark of Alzheimer's disease.
- miRNA-101a, acting through the MAPK pathway, regulates autophagy and may represent a novel mechanism in AD.
- miRNA-101a holds potential as a diagnostic biomarker and therapeutic target for Alzheimer's disease.