NR ATGC
AU Weiss,S.
TI The 37 kDa/67 kDa Laminin Receptor as a promising target for Therapy of Prion Diseases
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-33
PT Konferenz-Vortrag
AB
The 37kDa/67 kDa laminin receptor (LRP/LR) acts as the receptor for the cellular Prion Protein (PrPc) (1,2) and HSPGs (3,4) functions as co-factors/receptors for PrPc, respectively.
The laminin receptor is required for propagation of the Scrapie form of the prion protein PrPsc (5). Knock-down of the 37 kDa/67 kDa laminin receptor in mouse brain by a antisense LRP RNA strategy resulted in a significant reduction of LRP/LR levels in transgenic mouse brains (6).
The LRP/LR acts also as a receptor for PrPsc and polysulfated glycans such as the heparan sulfate mimetic HM2602 significantly reduce moPrP27-30 cell binding. Endocytosis of the infectious bovine PrPsc is mediated by LRP/LR apically expressed in human enterocytes, confirming that LRP/LR acts as the receptor for the infectious prion protein (7).
Selected single chain antibodies (scFvs) directed against the 37 kDa/67 kDa laminin receptor have been delivered to animals by injection of recombinant Adeno-Associated Viruses (AAVs) and by i.p. injection for passive immuno-therapy.
SiRNAs directed against LRP mRNA prohibit PrPsc propagation in cultured cells (5).
Recombinant lentiviruses expressing siRNAs directed against LRP mRNA have been used for delivery of siRNAs to scrapie infected mice.
scFvs directed against LRP/LR, siRNAs directed against LRP mRNA and the HM2602 represent alternative tools in therapy of prion diseases.
(1) Rieger et al. (1997) Nat. Med. 3, 1383-1388. (2) Gauczynski et al. (2001) EMBO J. 20, 5863-5875. (3) Hundt et al. (2001) EMBO J. 20, 5876-5886. (4) Warner et al. (2002) J. Biol. Chem. 277, 18421-18430. (5) Leucht et al. (2003) EMBO rep 4, 290-295. (6) Leucht et al. (2004) Transgenic Res 13, 81-85. (7) Morel et al. (2005) Am J Path, in press.
SP englisch
PO Deutschland