Increasing interest has recently been devoted to the study of transmissible spongiform encephalopathies (TSE) characterized by prion infections that culminate in fatal neurodegenerative disorders due to deposit of protein aggregates in the brain. According to Prusiner et al. [1-7] the mechanism of prion replication involves “normal” prions (cellular prion proteins, PrP C ) and “pathogenic” prions (PrP SC ). The disease is due to the propagation in the organism of the pathogenic conformer, which originates, by an autocatalytic mechanism, from the PrP C refolding. It is indeed the interaction between these two molecular entities that brings to a confor- mational change of the normal cellular prions that are converted into the pathological ones (reaction 1); while the molecular weight and the amino-acidic sequence are the same in both cases and are unaffected. PrP C + PrP SC → 2 PrP SC (1) PrP C is therefore necessary for both the development of the disease and the propagation of the pathogenic prions in the inoculated animals [8]. Although it has recently been demonstrated that the transition between the two prion conformers can occur reversibly in strongly denaturating media [9], the transition from the cellular to the pathogenic conformer, as well as the degree of advancement of the infection in the central nervous system are, both on thermodynamical basis [10] and from a pathological point of view, irreversible events. More specifically: a) the formation of pathogenic prions from cellular prions is an autocatalytic and cooperative process [1, 11], different from other controlled biological replication Some considerations on the kinetics of pathogenic prions formation Claudio BOTRÈ (a), Francesco BOTRÈ (b), Franco MAZZEI (c), Simona MONTILLA (a) and Elisabetta PODESTÀ (a) (a) Dipartimento di Farmacologia delle Sostanze Naturali e Fisiologia Generale, Università degli Studi “La Sapienza”, Rome, Italy (b) Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Rome, Italy (c) Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi “La Sapienza”, Rome, Italy Summary. - Literature data, respective to kinetics of infectivities due to prion diseases, have been here reconsidered. The autocatalytic phenomenon of prion replication and the process of advancement of the infection are also considered. A model describing the interconversion from “normal” into “pathogenic” prions, and the subsequent growth of the infection, is proposed. This model takes into account the existence of two different steps: the first, slower, in which the interaction between the two different prions, with the transformation of normal prions into the pathogen ones, takes place. The second one, very fast, in which the degree of advancement of the infection assumes the form of an irreversible, rapid trend. Key words: prion diseases, infectivity, kinetics, brain. Riassunto (Alcune considerazioni sulla cinetica di formazione di prioni patogeni). - Dati riportati in letteratura e relativi a cinetiche di infettività per patologie prioniche sono stati riconsiderati secondo un nuovo approccio. Sono discussi il processo autocatalitico, che è alla base della replicazione prionica, ed il processo di propagazione dell’infezione. Su questa base è proposto un modello cinetico che descrive l’interconversione, in due stadi, dei prioni dalla forma “normale” a quella “patogena” ed il conseguente sviluppo dell’infettività. Tale modello considera l’esistenza di due differenti fasi: la prima, più lenta, in cui si verifica l’interazione tra due diversi prioni, la seconda, molto più rapida, in cui il grado di avanzamento dell’infezione assume l’andamento tipico di un processo rapido con elevato grado di irreversibilità. Parole chiave: patologie prioniche, infettività, cinetiche, cervello. Indirizzo per la corrispondenza (Address for correspondence): Claudio Botrè, Dipartimento di Farmacologia delle Sostanze Naturali e Fisiolo- gia Generale, Università degli Studi “La Sapienza”, Piazzale Aldo Moro 5 - 00185 Roma. E-mail: botrec@uniroma1.it. Ann Ist Super Sanità 2002;38(2):195-198