The Anti-prion Activity of Congo Red

Abstract

PrP Sc , an abnormal conformational isoform of the normal prion protein, PrP C , is the only known component of the prion, a proteinacious agent that causes fatal neu-rodegenerative disorders in humans and other animals. The hallmark properties of PrP Sc are its insolubility in nondenaturing detergents and its resistance to digestion by proteases. Anions such as Congo red (CR) have been shown to reduce the accumulation of PrP Sc in a neuroblastoma cell line permanently infected with pri-ons as well as to delay disease onset in rodents when administrated prophylactically. The mechanism by which such anti-prion agents operate is unknown. We show here that in vitro incubation with CR renders native PrP Sc resistant to denaturation by boiling SDS. This resulted from PrP Sc conformation, since neither the properties of PrP C nor those of predenatured PrP Sc were changed by the addition of CR. CR-PrP Sc could only be denatured by the addition of acidic 3 M guani-dine thiocyanate. Since in vitro conversion experiments have suggested that partial denaturation may be required for PrP Sc to serve as template in the PrP C 3 PrP Sc conversion, we propose that CR inhibits prion propagation by overstabilizing the conformation of PrP Sc molecules.