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Title: miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease
Authors: Barros-Viegas, Ana Teresa 
Carmona, Vitor 
Ferreiro, Elisabete 
Guedes, Joana 
Cardoso, Ana Maria S. 
Cunha, Pedro 
Almeida, Luís Pereira de 
Oliveira, Catarina Resende de 
Magalhães, João Pedro de 
Peça, João 
Cardoso, Ana Luísa 
Keywords: Alzheimer’s disease; miR-31; gene therapy; lentiviral vector; APP; BACE1; amyloid-β peptide; cognitive function; memory
Issue Date: 6-Mar-2020
Publisher: Elsevier
Serial title, monograph or event: Molecular Therapy - Nucleic Acids
Volume: 19
Abstract: 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.
ISSN: 2162-2531
DOI: 10.1016/j.omtn.2020.01.010
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais

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