<P> The first hypothesis that tried to explain how prions replicate in a protein - only manner was the heterodimer model . This model assumed that a single PrP molecule binds to a single PrP molecule and catalyzes its conversion into PrP . The two PrP molecules then come apart and can go on to convert more PrP . However, a model of prion replication must explain both how prions propagate, and why their spontaneous appearance is so rare . Manfred Eigen showed that the heterodimer model requires PrP to be an extraordinarily effective catalyst, increasing the rate of the conversion reaction by a factor of around 10 . This problem does not arise if PrP exists only in aggregated forms such as amyloid, where cooperativity may act as a barrier to spontaneous conversion . What is more, despite considerable effort, infectious monomeric PrP has never been isolated . </P> <P> An alternative model assumes that PrP exists only as fibrils, and that fibril ends bind PrP and convert it into PrP . If this were all, then the quantity of prions would increase linearly, forming ever longer fibrils . But exponential growth of both PrP and of the quantity of infectious particles is observed during prion disease . This can be explained by taking into account fibril breakage . A mathematical solution for the exponential growth rate resulting from the combination of fibril growth and fibril breakage has been found . The exponential growth rate depends largely on the square root of the PrP concentration . The incubation period is determined by the exponential growth rate, and in vivo data on prion diseases in transgenic mice match this prediction . The same square root dependence is also seen in vitro in experiments with a variety of different amyloid proteins . </P> <P> The mechanism of prion replication has implications for designing drugs . Since the incubation period of prion diseases is so long, an effective drug does not need to eliminate all prions, but simply needs to slow down the rate of exponential growth . Models predict that the most effective way to achieve this, using a drug with the lowest possible dose, is to find a drug that binds to fibril ends and blocks them from growing any further . </P> <Table> Diseases caused by prions <Tr> <Th> Affected animal (s) </Th> <Th> Disease </Th> </Tr> <Tr> <Td> sheep, goat </Td> <Td> Scrapie </Td> </Tr> <Tr> <Td> cattle </Td> <Td> Bovine spongiform encephalopathy (BSE), mad cow disease </Td> </Tr> <Tr> <Td> mink </Td> <Td> Transmissible mink encephalopathy (TME) </Td> </Tr> <Tr> <Td> white - tailed deer, elk, mule deer, moose </Td> <Td> Chronic wasting disease (CWD) </Td> </Tr> <Tr> <Td> cat </Td> <Td> Feline spongiform encephalopathy (FSE) </Td> </Tr> <Tr> <Td> nyala, oryx, greater kudu </Td> <Td> Exotic ungulate encephalopathy (EUE) </Td> </Tr> <Tr> <Td> ostrich </Td> <Td> Spongiform encephalopathy (Has not been shown to be transmissible .) </Td> </Tr> <Tr> <Td> human </Td> <Td> Creutzfeldt--Jakob disease (CJD) </Td> </Tr> <Tr> <Td> Iatrogenic Creutzfeldt--Jakob disease (iCJD) </Td> </Tr> <Tr> <Td> Variant Creutzfeldt--Jakob disease (vCJD) </Td> </Tr> <Tr> <Td> Familial Creutzfeldt--Jakob disease (fCJD) </Td> </Tr> <Tr> <Td> Sporadic Creutzfeldt--Jakob disease (sCJD) </Td> </Tr> <Tr> <Td> Gerstmann--Sträussler--Scheinker syndrome (GSS) </Td> </Tr> <Tr> <Td> Fatal familial insomnia (FFI) </Td> </Tr> <Tr> <Td> Kuru </Td> </Tr> <Tr> <Td> Familial spongiform encephalopathy </Td> </Tr> <Tr> <Td> Multiple System Atrophy (MSA): Not a TSE and is not by typical prions Prp / PrP but by a misfolded α - Synuclein . </Td> </Tr> </Table>

How do inorganic acids act as denaturing agent for proteins