Related Experiment Video
Updated: Oct 2, 2025
06:59
Isolation and Profiling of MicroRNA-containing Exosomes from Human Bile
Published on: June 13, 2016
10.5K
Exosomes Mediate APP Dysregulation via APP-miR-185-5p Axis
Lu Ding1, Xiaoyu Yang1, Xiaohuan Xia1,2,3,4
1Department of Anesthesiology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Frontiers in Cell and Developmental Biology
|February 28, 2022
Summary
Alzheimer's disease (AD) pathology involves amyloid precursor protein (APP) misexpression. Exosomes from AD brains promote APP expression, mediated by reduced miR-185-5p, a potential AD biomarker.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Amyloid precursor protein (APP) misexpression is a key factor in Alzheimer's disease (AD) pathogenesis.
- The regulatory mechanisms of APP expression in pathological conditions are not fully understood.
Purpose of the Study:
- To investigate the role of exosomes in regulating APP expression in Alzheimer's disease.
- To identify the specific molecular mechanisms involved in exosome-mediated APP regulation.
Main Methods:
- Isolation of exosomes from AD mouse brains and neuronal N2a cells.
- Analysis of APP and miR-185-5p expression in recipient cells.
- Investigation of the interaction between APP 3'UTR and miR-185-5p.
- Quantification of exosomal miR-185-5p in AD patients and mice.
Main Results:
- Exosomes from AD mouse brains promoted APP expression in neuronal cells.
- Exosomes overexpressing APP (APP-EXO) induced APP dysregulation.
- APP-EXO effects were mediated by reduced exosomal miR-185-5p, not direct APP transfer.
- miR-185-5p binds to APP 3'UTR, inhibiting its exosomal sorting.
- Reduced exosomal miR-185-5p in exosomes mimicked APP-EXO effects.
- Serum exosomal miR-185-5p was significantly decreased in AD patients and mice.
Conclusions:
- A novel exosome-dependent mechanism regulates APP expression.
- Reduced exosomal miR-185-5p is implicated in AD pathogenesis.
- Exosomes and exosomal miRNAs represent potential therapeutic targets and diagnostic biomarkers for AD.
Related Concept Videos
01:36Overview of Exosomes
2.9K
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
2.9K
01:22MicroRNAs
3.2K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.2K
01:17The Extrinsic Apoptotic Pathway
6.7K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.7K
01:15Receptor Downregulation in MVBs
2.2K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.2K
01:37The Unfolded Protein Response
5.2K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.2K
01:31Regulation of the Unfolded Protein Response
2.6K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K