NR ATNS
AU Vana,K.; Weiss,S.
TI Transdominant negative LRP/LR mutants as alternative therapeutic tools in TSEs
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-16
PT Konferenz-Poster
AB
The 37/ 67 kDa laminin receptor (LRP/LR) acts as the cell surface receptor for the cellular prion protein PrPc1. Heparan sulfate proteoglycans (HSPGs) - binding partners of the prion protein2 - were identified as co-factors/ co-receptors for the binding of PrPc to LRP/LR3. Secretion of a transmembrane deletion mutant of LRP/LR (LRPdelTMD) from BHK cells transfected with recombinant Semliki-Forest-Virus (SFV) RNAs prevented PrPc binding and internalization1. A LRP mutant encompassing the extracellular domain (LRP102-295) was efficiently secreted from N2a and ScN2a cells and reduced significantly PrPc binding to N2a cells as well as PrPsc propagation in ScN2a cells. These results suggest that LRP 102-295 may act as a decoy mutant by trapping PrP molecules. Expression of the LRP102-295 mutant in scrapie infected mice might also reduce or abolish PrPsc propagation in vivo. Therefore, the mutant might represent an auspicious tool for 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
AD K.Vana, S.Weiss, Genzentrum-Institut für Biochemie der LMU Muenchen, Feodor-Lynen-Str.25, D-81377 Munich, Germany
SP englisch
PO Deutschland