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Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
MicroRNAs in Extracellular Vesicles of Alzheimer's Disease
1State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disease with dysfunction of memory, language and thinking. More than 55 million people were diagnosed with AD or other dementia around the world in 2020. The pathology of AD is still unclear and there are no applicable therapies for AD. MicroRNAs (miRNAs) play key roles in AD pathology and have great potential for the diagnosis and treatment of AD. Extracellular vesicles (EVs) widely exist in body fluids such as blood and cerebrospinal fluid (CSF) and contain miRNAs that are involved in cell-to-cell communication. We summarized the dysregulated miRNAs in EVs derived from the different body fluids of AD patients, as well as their potential function and application in AD. We also compared these dysregulated miRNAs in EVs to those in the brain tissues of AD patients aiming to provide a comprehensive view of miRNAs in AD. After careful comparisons, we found that miR-125b-5p and miR-132-3p were upregulated and downregulated in several different brain tissues of AD and EVs of AD, respectively, suggesting their value in AD diagnosis based on EV miRNAs. Furthermore, miR-9-5p was dysregulated in EVs and different brain tissues of AD patients and had also been tested as a potential therapy for AD in mice and human cell models, suggesting that miR-9-5p could be used to design new therapies for AD.
Insights
Alzheimer's disease (AD) research highlights microRNAs (miRNAs) in extracellular vesicles (EVs) as potential diagnostic biomarkers. Specific miRNAs show promise for both diagnosing and treating this neurodegenerative disease.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Alzheimer's disease (AD) affects over 55 million globally, characterized by cognitive decline, with unclear pathology and limited therapies.
- MicroRNAs (miRNAs) are implicated in AD pathogenesis and hold potential for diagnosis and treatment.
- Extracellular vesicles (EVs) in bodily fluids contain miRNAs involved in intercellular communication, offering a source for biomarker discovery.
Purpose of the Study:
- To review dysregulated miRNAs within EVs from Alzheimer's disease patients.
- To assess the function and application of EV-derived miRNAs in AD.
- To compare EV miRNAs with those in brain tissue for a comprehensive AD miRNA landscape.
Main Methods:
- Systematic review of dysregulated miRNAs in EVs from various body fluids of AD patients.
- Comparative analysis of EV miRNAs against miRNAs found in AD brain tissues.
- Evaluation of identified miRNAs for diagnostic and therapeutic potential in AD models.
Main Results:
- Specific miRNAs, including miR-125b-5p and miR-132-3p, showed differential expression in AD brain tissues and EVs, indicating diagnostic value.
- miR-9-5p was dysregulated in both EVs and brain tissues and demonstrated therapeutic potential in preclinical AD models.
- EV-derived miRNAs offer a promising avenue for non-invasive AD diagnosis and targeted therapy development.
Conclusions:
- EV-derived miRNAs represent valuable biomarkers for Alzheimer's disease diagnosis.
- miR-9-5p shows potential as a therapeutic target for Alzheimer's disease.
- Further research into EV miRNAs can advance AD diagnostics and therapeutics.
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