NR AREX
AU Vana,K.; Töpper,D.; Weiss,S.
TI Small interfering (si) RNAs directed against LRP mRNA as anti-prion tools and their delievery by lentiviral vectors
QU TSE-Forum, 4. Kongress - Nationale TSE-Forschungsplattform, Düsseldorf 28.10.-29.10.2004, Poster THE-07
PT Konferenz-Poster
AB
Transmissible spongiform encephalopaties (TSEs) are neurodegenerative diseases, which include Scrapie in sheep, bovine spongiform encephalopathie (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. Prions, the causative agents of TSEs, are known to interact with the cellular prion protein (PrPc) by inducing conformational changes in the prion protein. The 37kDa/ 67kDa laminin receptor (LRP/ LR) acts as the cell surface receptor for the cellular prion protein1. Heparan sulfate proteoglycans (HSPGs) - binding partners of the prion protein2 - were identified as co-factors/ co-receptors for PrPc3 (for review see 4). It has been shown that LRP/ LR is essential for PrPres propagation in neuronal cells5. The accumulation of PrPsc in scrapie-infected neuronal cells (ScN2a) has been prevented by transfection with small interfering (si) RNAs specific for the LRPmRNA5. These results demonstrate the necessity of the laminin receptor (LRP/ LR) for PrPsc propagation in cultured cells. Vector-based application of siRNAs circumvents the transient effect of down-regulation of gene expression and allows persistent suppression and therefore analysis of loss-of-function phenotypes that develop over longer periods of time. By the use of a lentiviral-based expression system more efficient delivery of short hairpin RNA (shRNA) to mammalian cells in culture or in vivo becomes possible and suggests that siRNAs directed against the LRP mRNA could be used as therapeutical tool in the treatment of TSEs.
1 Gauczynski et al., EMBO J., 2001, 20, 5863-75
2 Warner et al., J.Biol.Chem., 2002, 277, 18421-18430
3 Hundt et al., EMBO J., 2001, 20, 5876-86
4 Gauczynski et al., Adv.Protein Chem., 2001, 57, 229-72
5 Leucht et al., EMBO reports, 2003, 4, 290-5
AD K. Vana, D. Töpper and S. Weiss, Laboratorium für Molekulare Biologie - Genzentrum - Institut für Biochemie der LMU München, Feodor-Lynen-Straße 25, 81377 München, Germany
SP englisch
PO Deutschland
OR Tagungsband