miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease
Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive memory impairment, behavioral changes, and, ultimately, loss of consciousness and death. Recently, microRNA (miRNA) dysfunction has been associated with increased production and impaired clearan...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Book |
| Published: |
Elsevier,
2020-03-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
MARC
| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_0a6fe9c2a19a4a2f9dc6dd4e1645a878 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Ana Teresa Barros-Viegas |e author |
| 700 | 1 | 0 | |a Vítor Carmona |e author |
| 700 | 1 | 0 | |a Elisabete Ferreiro |e author |
| 700 | 1 | 0 | |a Joana Guedes |e author |
| 700 | 1 | 0 | |a Ana Maria Cardoso |e author |
| 700 | 1 | 0 | |a Pedro Cunha |e author |
| 700 | 1 | 0 | |a Luís Pereira de Almeida |e author |
| 700 | 1 | 0 | |a Catarina Resende de Oliveira |e author |
| 700 | 1 | 0 | |a João Pedro de Magalhães |e author |
| 700 | 1 | 0 | |a João Peça |e author |
| 700 | 1 | 0 | |a Ana Luísa Cardoso |e author |
| 245 | 0 | 0 | |a miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease |
| 260 | |b Elsevier, |c 2020-03-01T00:00:00Z. | ||
| 500 | |a 2162-2531 | ||
| 500 | |a 10.1016/j.omtn.2020.01.010 | ||
| 520 | |a Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive memory impairment, behavioral changes, and, ultimately, loss of consciousness and death. Recently, microRNA (miRNA) dysfunction has been associated with increased production and impaired clearance of amyloid-β (Aβ) peptides, whose accumulation is one of the most well-known pathophysiological markers of this disease. In this study, we identified several miRNAs capable of targeting key proteins of the amyloidogenic pathway. The expression of one of these miRNAs, miR-31, previously found to be decreased in AD patients, was able to simultaneously reduce the levels of APP and Bace1 mRNA in the hippocampus of 17-month-old AD triple-transgenic (3xTg-AD) female mice, leading to a significant improvement of memory deficits and a reduction in anxiety and cognitive inflexibility. In addition, lentiviral-mediated miR-31 expression significantly ameliorated AD neuropathology in this model, drastically reducing Aβ deposition in both the hippocampus and subiculum. Furthermore, the increase of miR-31 levels was enough to reduce the accumulation of glutamate vesicles in the hippocampus to levels found in non-transgenic age-matched animals. Overall, our results suggest that miR-31-mediated modulation of APP and BACE1 can become a therapeutic option in the treatment of AD. Keywords: Alzheimer's disease, miR-31, gene therapy, lentiviral vector, APP, BACE1, amyloid-β peptide, cognitive function, memory | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Molecular Therapy: Nucleic Acids, Vol 19, Iss , Pp 1219-1236 (2020) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2162253120300457 | |
| 787 | 0 | |n https://doaj.org/toc/2162-2531 | |
| 856 | 4 | 1 | |u https://doaj.org/article/0a6fe9c2a19a4a2f9dc6dd4e1645a878 |z Connect to this object online. |