[Prions and proteinaceous proteinase inhibitors: structural analogs and their consequences. II. Dynamics of prion diseases].
The assumption about pathogenic prions as the proteins supplying the extracellular proteinases transport into intracellular space permits to bring the pathogenesis of prion diseases to order of the known and partially proved process regarding the case of prion diseases. We present the mathematical model of the dynamics of prion pathogenesis explaining the existence of the minimal infectious dose and small influence of its exceeding on the duration of long-term latent period of the disease. According to the model proposed the transformation of the neuronal cell into PrPSc breeder is the result of proteolytic damage of shaperoning system caused by accumulation in the cell of some crucial amount of proteinase-transporting prions. Such an accumulation is considered as the result of successive and centripheral lay-by-lay transformation of compact cellular locus from higher affinity to prions to normal one. The formation in the moveable frontier lays of the wave with high prion consisting and its closing into the locus center leads to dramatic splash of prion concentration even at moderate difference between higher and normal affinity levels. The final concentration of prions depends mainly on the correlation between these affinities whilst on exceeding of some value the dimension of the locus is of no importance.
Verevka
S V
SV
Palladin Institute of Biochemistry, NAS of Ukraine, Kyiv. verevka@biochem.kiev.ua
D008968:Molecular Conformation; D009474:Neurons / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism / Q000503:physiopathology*; D011328:Prions / Q000737:chemistry / Q000502:physiology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism*
D011328:Prions; D011480:Protease Inhibitors