| Abstract | Accumulation of insoluble aggregates of beta-amyloid peptide, a cleavage product of amyloid precursor protein, is thought to be a central step in the pathogenesis of Alzheimer's disease. The major enzymes required for the generation of toxic amyloid-beta peptide are beta-(BACE1) and gamma-secretases. Here, we present the rational design and the application of synthetic and lentivirus vector-encoded siRNAs for specific and efficient knockdown of overexpressed and endogenous BACE1, both in dividing and neural stem cells and in a rat brain. We also tested an approach to anti-amyloid therapy by the use of the allele-specific siRNAs to silence the mutant presenilin 1 (L392V PS-1), the main component of gamma-secretase, responsible for development of Familial Alzheimer's disease. Reducing the level of beta-amyloid accumulation in the brain could be beneficial for metabolic studies as well as potential therapeutic approach for prevention and treatment of Alzheimer's disease. |
| Authors | Malgorzata Sierant, Katarzyna Kubiak, Julia Kazmierczak-Baranska, Alina Paduszynska, Tomoko Kuwabara, Masaki Warashina, Benedetta Nacmias, Sandro Sorbi, Barbara Nawrot
(Affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.)
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| Journal | Nucleic acids symposium series (2004)
(Nucleic Acids Symp Ser (Oxf))
Issue 52
Pg. 41-2
( 2008)
ISSN: 1746-8272 England |
| PMID | 18776243
(Publication Type: Journal Article)
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