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International Journal of Alzheimer’s Disease
Volume 2012, Article ID 947147, 12 pages
Research Article

Silencing of Amyloid Precursor Protein Expression Using a New Engineered Delta Ribozyme

1Département de Psychiatrie-Neurosciences, Faculté de Médecine, Unviersité Laval et Neurosciences CHUL, 2705 Laurier, Québec, QC, Canada G1V 4G2
2RNA Group/Groupe ARN, Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001 12th Avenue, Sherbrooke, QC, Canada J1H 5N4

Received 30 May 2011; Accepted 1 November 2011

Academic Editor: Anton P. Porsteinsson

Copyright © 2012 Manel Ben Aissa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer's disease (AD) etiological studies suggest that an elevation in amyloid-β peptides (Aβ) level contributes to aggregations of the peptide and subsequent development of the disease. The major constituent of these amyloid peptides is the 1 to 40–42 residue peptide (Aβ40−42) derived from amyloid protein precursor (APP). Most likely, reducing Aβ levels in the brain may block both its aggregation and neurotoxicity and would be beneficial for patients with AD. Among the several possible ways to lower Aβ accumulation in the cells, we have selectively chosen to target the primary step in the Aβ cascade, namely, to reduce APP gene expression. Toward this end, we engineered specific SOFA-HDV ribozymes, a new generation of catalytic RNA tools, to decrease APP mRNA levels. Additionally, we demonstrated that APP-ribozymes are effective at decreasing APP mRNA and protein levels as well as Aβ levels in neuronal cells. Our results could lay the groundwork for a new protective treatment for AD.