miRNA-31 Improves Cognition and Abolishes Amyloid-beta Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Barros Viegas, AT (Author) Other; Carmona, V (Author) Other; Ferreiro, E (Author) Other; Guedes, J (Author) Other; Cardoso, AM (Author) Other; Cunha, P (Author) Other; de Almeida, LP (Author) Other; de Oliveira, CR (Author) Other; de Magalhaes, JP (Author) Other; Peca, J (Author) Other; Cardoso, AL (Author) Other

Journal

Title: Molecular Therapy - Nucleic Acids

Vol. 19

Pages: 1219-1236

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 43 Citations

Scopus - 48 Citations

Other information

Authenticus ID: P-00R-QGW

DOI: 10.1016/j.omtn.2020.01.010

Abstract (EN): 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-beta (A beta) 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 A beta 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 miR31-mediated modulation of APP and BACE1 can become a therapeutic option in the treatment of AD.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 18