NR AJPZ
AU Proske,D.; Gilch,S.; Wopfner,F.; Schätzl,H.M.; Winnacker,E.L.; Famulok,M.
TI Prion-protein-specific aptamer reduces PrPsc formation
QU Chembiochem : a European Journal of Chemical Biology 2002 Aug 2; 3(8): 717-25
PT journal article
AB The critical initial event in the pathophysiology of transmissible spongiform encephalopathies (TSEs) appears to be the conversion of the cellular prion protein (PrPc) into the abnormal isoform PrPsc. This isoform forms high-molecular-weight protease K (PK) resistant aggregates that accumulate in the central nervous system of affected individuals. We have selected nuclease-resistant 2'-amino-2'-deoxypyrimidine-modified RNA aptamers which recognize a peptide comprising amino acid residues 90-129 of the human prion protein with high specificity. This domain of prion proteins is thought to be functionally important for the conversion of PrPc into its pathogenic isoform PrPsc and is highly homologous among prion proteins of various species including mouse, hamster, and man. Consequently, aptamer DP7 binds to the full-length human, mouse, and hamster prion protein. At low concentrations in the growth medium of persistently prion-infected neuroblastoma cells, aptamer DP7 significantly reduced the relative proportion of de novo synthesized PK-resistant PrPsc within only 16 h. These findings may open the door towards a rational development of a new class of drugs for the therapy or prophylaxis of prion diseases.
AD Institut für Biochemie, Genzentrum der LMU München, Feodor-Lynen-Strasse 25, 81377 München (Germany).
SP englisch
PO Deutschland