Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.00564/full |
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| author | Yavar Jahangard Hamideh Monfared Arman Moradi Meysam Zare Javad Mirnajafi-Zadeh Seyed Javad Mowla |
| author_facet | Yavar Jahangard Hamideh Monfared Arman Moradi Meysam Zare Javad Mirnajafi-Zadeh Seyed Javad Mowla |
| author_sort | Yavar Jahangard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T15:38:36Z |
| format | Article |
| id | doaj.art-1418ded3abb54d0ab4d23e3e6a4b5f50 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-10T15:38:36Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-1418ded3abb54d0ab4d23e3e6a4b5f502022-12-22T01:43:10ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-06-011410.3389/fnins.2020.00564538428Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s DiseaseYavar Jahangard0Hamideh Monfared1Arman Moradi2Meysam Zare3Javad Mirnajafi-Zadeh4Seyed Javad Mowla5Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranAlzheimer 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.https://www.frontiersin.org/article/10.3389/fnins.2020.00564/fullAlzheimer’s diseasemiR-29exosomesBACE1BIM |
| spellingShingle | Yavar Jahangard Hamideh Monfared Arman Moradi Meysam Zare Javad Mirnajafi-Zadeh Seyed Javad Mowla Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease Frontiers in Neuroscience Alzheimer’s disease miR-29 exosomes BACE1 BIM |
| title | Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease |
| title_full | Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease |
| title_fullStr | Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease |
| title_full_unstemmed | Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease |
| title_short | Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer’s Disease |
| title_sort | therapeutic effects of transplanted exosomes containing mir 29b to a rat model of alzheimer s disease |
| topic | Alzheimer’s disease miR-29 exosomes BACE1 BIM |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.00564/full |
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