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Barros-Viegas AT, Carmona V, Ferreiro E, et al. miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease. Mol Ther Nucleic Acids. 2020;19:1219-1236doi: 10.1016/j.omtn.2020.01.010.
Barros-Viegas, A. T., Carmona, V., Ferreiro, E., Guedes, J., Cardoso, A. M., Cunha, P., Pereira de Almeida, L., Resende de Oliveira, C., Pedro de Magalhães, J., Peça, J., & Cardoso, A. L. (2020). miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease. Molecular therapy. Nucleic acids, 191219-1236. https://doi.org/10.1016/j.omtn.2020.01.010
Barros-Viegas, Ana Teresa, et al. "miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease." Molecular therapy. Nucleic acids vol. 19 (2020): 1219-1236. doi: https://doi.org/10.1016/j.omtn.2020.01.010
Barros-Viegas AT, Carmona V, Ferreiro E, Guedes J, Cardoso AM, Cunha P, Pereira de Almeida L, Resende de Oliveira C, Pedro de Magalhães J, Peça J, Cardoso AL. miRNA-31 Improves Cognition and Abolishes Amyloid-β Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease. Mol Ther Nucleic Acids. 2020 Mar 06;19:1219-1236. doi: 10.1016/j.omtn.2020.01.010. Epub 2020 Jan 17. PMID: 32069773; PMCID: PMC7031139.
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Mol Ther Nucleic Acids. 2020 Mar 06;19:1219-1236. doi: 10.1016/j.omtn.2020.01.010. Epub 2020 Jan 17.

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

Molecular therapy. Nucleic acids

Ana Teresa Barros-Viegas, Vítor Carmona, Elisabete Ferreiro, Joana Guedes, Ana Maria Cardoso, Pedro Cunha, Luís Pereira de Almeida, Catarina Resende de Oliveira, João Pedro de Magalhães, João Peça, Ana Luísa Cardoso

Affiliations

  1. Doctoral Programme in Health Sciences, Faculty of Medicine, University of Coimbra, Coimbra, 3000-548, Portugal; CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
  2. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
  3. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal.
  4. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
  5. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
  6. Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, United Kingdom.
  7. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal.
  8. CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3030-789 Coimbra, Portugal. Electronic address: [email protected].

PMID: 32069773 PMCID: PMC7031139 DOI: 10.1016/j.omtn.2020.01.010

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.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: APP; Alzheimer’s disease; BACE1; amyloid-β peptide; cognitive function; gene therapy; lentiviral vector; memory; miR-31

References

  1. J Exp Med. 2018 Mar 5;215(3):927-940 - PubMed
  2. Am J Psychiatry. 2006 Dec;163(12):2164-9 - PubMed
  3. J Biol Chem. 2002 Oct 25;277(43):40919-29 - PubMed
  4. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15751-6 - PubMed
  5. Prog Mol Biol Transl Sci. 2017;146:127-171 - PubMed
  6. Genome Biol. 2010;11(8):R90 - PubMed
  7. Mol Cell Neurosci. 2015 May;66(Pt A):3-11 - PubMed
  8. J Alzheimers Dis. 2018;62(2):523-547 - PubMed
  9. Brain. 1952 Sep;75(3):408-27 - PubMed
  10. J Neuroendocrinol. 1995 Jun;7(6):475-82 - PubMed
  11. Neurol Neurochir Pol. 2017 Nov - Dec;51(6):537 - PubMed
  12. J Alzheimers Dis. 2012;30(2):355-65 - PubMed
  13. Front Neurosci. 2014 Apr 21;8:83 - PubMed
  14. J Neurosci. 2014 Sep 3;34(36):11929-47 - PubMed
  15. EMBO Mol Med. 2013 Oct;5(10):1613-34 - PubMed
  16. J Neurosci. 2008 Jan 30;28(5):1213-23 - PubMed
  17. Arch Med Res. 2012 Nov;43(8):595-9 - PubMed
  18. Prog Neurobiol. 2001 Jun;64(2):129-55 - PubMed
  19. Nature. 2009 Jul 23;460(7254):479-86 - PubMed
  20. Neurobiol Dis. 2009 Mar;33(3):422-8 - PubMed
  21. Biol Psychiatry. 1997 Dec 1;42(11):1030-8 - PubMed
  22. Mol Neurodegener. 2014 Nov 18;9:51 - PubMed
  23. Nat Methods. 2015 Aug;12(8):697 - PubMed
  24. Eur J Neurosci. 2015 May;41(9):1245-62 - PubMed
  25. Science. 1992 Apr 10;256(5054):184-5 - PubMed
  26. Science. 2016 May 6;352(6286):712-716 - PubMed
  27. Science. 2004 Apr 23;304(5670):594-6 - PubMed
  28. Trends Neurosci. 2009 Apr;32(4):199-206 - PubMed
  29. PLoS One. 2011;6(10):e23721 - PubMed
  30. Cortex. 2015 Jun;67:83-94 - PubMed
  31. Front Genet. 2014 Feb 18;5:23 - PubMed
  32. Genome Res. 2013 Apr;23(4):604-15 - PubMed
  33. Behav Brain Res. 2004 Jun 4;152(1):23-34 - PubMed
  34. Neurobiol Dis. 2001 Jun;8(3):433-46 - PubMed
  35. Compr Physiol. 2016 Mar 15;6(2):603-21 - PubMed
  36. Alzheimers Res Ther. 2014 Oct 27;6(5):73 - PubMed
  37. RNA. 2009 Feb;15(2):287-93 - PubMed
  38. PLoS One. 2010 Feb 01;5(2):e8898 - PubMed
  39. J Anat. 2005 Sep;207(3):271-82 - PubMed
  40. J Biol Chem. 2009 Jan 23;284(4):1971-81 - PubMed
  41. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6415-20 - PubMed
  42. Nat Struct Mol Biol. 2011 Sep 11;18(10):1139-46 - PubMed
  43. Neurology. 2001 Apr 24;56(8):1094-8 - PubMed
  44. Alzheimers Dement. 2010 Mar;6(2):158-94 - PubMed
  45. Cell. 2010 Apr 2;141(1):129-41 - PubMed
  46. J Neurosci. 2011 Feb 2;31(5):1773-9 - PubMed
  47. Nat Protoc. 2006;1(1):7-12 - PubMed
  48. Nature. 2018 Aug;560(7718):291-292 - PubMed
  49. J Neurochem. 2008 May;105(3):584-94 - PubMed
  50. J Biomol Screen. 2013 Apr;18(4):453-61 - PubMed
  51. Curr Opin Neurol. 2016 Feb;29 Suppl 1:S27-35 - PubMed
  52. Neurobiol Aging. 2008 Nov;29(11):1619-30 - PubMed
  53. J Alzheimers Dis. 2006;9(3 Suppl):101-15 - PubMed
  54. Dis Markers. 2015;2015:625659 - PubMed
  55. J Neurosci. 2011 Oct 12;31(41):14820-30 - PubMed
  56. Cogn Process. 2012 May;13(2):93-110 - PubMed
  57. Cell. 2011 Sep 30;147(1):235-46 - PubMed
  58. Nat Rev Drug Discov. 2011 Aug 19;10(9):698-712 - PubMed
  59. Hum Mol Genet. 2014 Dec 1;23(23):6286-301 - PubMed
  60. Arq Neuropsiquiatr. 2008 Sep;66(3B):619-24 - PubMed
  61. Nucleic Acids Res. 2013 Jul;41(Web Server issue):W169-73 - PubMed
  62. Neurobiol Aging. 2003 Dec;24(8):1029-46 - PubMed
  63. J Alzheimers Dis. 2014;39(1):89-101 - PubMed
  64. Neuron. 2003 Jul 31;39(3):409-21 - PubMed
  65. Acta Neuropathol. 2011 Feb;121(2):193-205 - PubMed
  66. J Alzheimers Dis. 2008 May;14(1):27-41 - PubMed
  67. Genet Med. 2011 Jun;13(6):597-605 - PubMed

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