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Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease
- Source :
- Frontiers in Neuroscience, Vol 14 (2020), Frontiers in Neuroscience
- Publication Year :
- 2020
- Publisher :
- Frontiers Media SA, 2020.
-
Abstract
- Alzheimer disease (AD) is a complex neurodegenerative disorder with no definite treatment. The expression of miR-29 family is significantly reduced in AD, suggesting a part for the family members in pathogenesis of the disease. The recent emergence of microRNA (miRNA)–based therapeutic approaches is emphasized on the efficiency of miRNA transfer to target cells. The endogenously made secretory vesicles could provide a biological vehicle for drug delivery. Characteristics such as small sizes, the ability to cross the blood–brain barrier, the specificity in binding to the right target cells, and most importantly the capacity to be engineered as drug carriers have made exosomes desirable vehicles to deliver genetic materials to the central nervous system. Here, we transfected rat bone marrow mesenchymal stem cells and HEK-293T cells (human embryonic kidney 293 cells) with recombinant expression vectors, carrying either mir-29a or mir-29b precursor sequences. A significant overexpression of miR-29 and downregulation of their targets genes, BACE1 (β-site amyloid precursor protein cleaving enzyme 1) and BIM [Bcl−2 interacting mediator of cell death (BCL2-like 11)], were confirmed in the transfected cells. Then, we confirmed the packaging of miR-29 in exosomes secreted from the transfected cells. Finally, we investigated a possible therapeutic effect of the engineered exosomes to reduce the pathological effects of amyloid-β (Aβ) peptide in a rat model of AD. Aβ–treated model rats showed some deficits in spatial learning and memory. However, in animals injected with miR-29–containing exosomes at CA1 (cornu ammonis area), the aforementioned impairments were prevented. In conclusion, our findings provide a new approach for the packaging of miR-29 in exosomes and that the engineered exosomes might have a therapeutic potential in AD.
- Subjects :
- 0301 basic medicine
Programmed cell death
miR-29
exosomes
lcsh:RC321-571
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
microRNA
Amyloid precursor protein
BIM
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Original Research
biology
General Neuroscience
Mesenchymal stem cell
HEK 293 cells
BACE1
Transfection
Microvesicles
Cell biology
030104 developmental biology
biology.protein
Alzheimer’s disease
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- ISSN :
- 1662453X
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Frontiers in Neuroscience
- Accession number :
- edsair.doi.dedup.....00a8c1ed4d3e4581d08614d4f0bf7bd1