THE ANTI-PRION ACTIVITY OF CONGO RED - PUTATIVE MECHANISM

PrPSc, an abnormal conformational isoform of the normal prion protein, PrPC, is the only known component of the prion, a proteinacious agent that causes fatal neurodegenerative disorders in humans and other ani mals. The hallmark properties of PrPSc are its insolubility in nondena turing detergents and its resistance to digestion by proteases. Anions such as Congo red (CR) have been shown to reduce the accumulation of PrPSc in a neuroblastoma cell line permanently infected with prions as well as to delay disease onset in rodents when administrated prophyla ctically. The mechanism by which such anti prion agents operate is unk nown. We show here that in vitro incubation with CR renders native PrP Sc resistant to denaturation by boiling SDS, This resulted from PrPSc conformation, since neither the properties of PrPC nor those of preden atured PrPSc were changed by the addition of CR. CR-PrPSc could only b e denatured by the addition of acidic 3 M guanidine thiocyanate. Since in vitro conversion experiments have suggested that partial denaturat ion may be required for PrPSc to serve as template in the PrPC --> PrP Sc conversion, we propose that CR inhibits prion propagation by overst abilizing the conformation of PrPSc molecules.