title: Silencing of amyloid precursor protein expression using a new engineered delta ribozyme.
abstract: 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 (Aβ(40-42)) 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.
authors.affiliation: Département de Psychiatrie-Neurosciences, Faculté de Médecine, Unviersité Laval et Neurosciences CHUL, 2705 Laurier, Québec, QC, Canada G1V 4G2.
authors.forename: Manel
authors.initials: M
authors.lastname: Ben Aissa
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: April
authors.forename: Lucien-Junior
authors.initials: LJ
authors.lastname: Bergeron
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Perreault
authors.forename: Georges
authors.initials: G
authors.lastname: Levesque