Table 2.
PMCA studies of prion biology
| Prion biology | Study | PMCA seeds | PMCA substrates | Summary |
|---|---|---|---|---|
| Prion hypothesis | Castilla et al. (2005a) | 263 K | Normal hamster brain homogenate | PMCA-amplified PrPres induces bona fide prion disease in wild-type hamsters |
| Deleault et al. (2007) | Purified Sc237, purified 139H, or no seed | Purified hamster PrPC with co-purified lipids, plus RNA cofactor | Generation of infectious PrPSc from purified PrPC requires RNA cofactor in either seeded or non-seeded PMCA reactions | |
| Wang et al. (2010, 2015), Pan et al. (2020) | No seed | Bacterially expressed and purified recombinant mouse PrP, plus lipid and RNA cofactors | De novo formation of infectious recombinant prion by PMCA requires lipid and RNA cofactors | |
| Prion strain | Castilla et al. (2008b) | 5 murine prion strains, 4 human prion strains | Normal mouse brain homogenate, brain homogenate from transgenic mice expressing human PrP | PMCA-amplified prions faithfully recapitulate the strain-specific biochemical and biological properties of the seed prion strains |
| Wang et al. (2010), Kim et al. (2010), Deleault et al. (2012b) | No seed, mouse prion, or hamster prion | Recombinant mouse or hamster PrP | PMCA generated infectious recombinant prions manifest novel strain characteristics, which demonstrates the critical role of in vivo cofactors in maintaining strain properties | |
| Prion species barrier | Castilla et al. (2008a) | Mouse and hamster prions | Normal mouse and hamster brain homogenates | PMCA not only recapitulates the species barrier phenomenon in vitro, but also demonstrates its great potential to investigate strain adaptation and stabilization |
| Green et al. (2008) | Mouse prion | Brain homogenate from transgenic mice expressing deer PrP | PMCA-facilitated strain adaptation recapitulates the in vivo cross-species transmission that requires hundreds of days of adaptation and stabilization | |
| Pritzkow (2022) | North American CWD and Norwegian CWD prions | Normal mouse brain homogenate, brain homogenates from transgenic mice expressing PrP of various species | Inter-species PMCA studies suggest North American and Norwegian CWD prions represent different strains with distinct cross-species conversion potentials | |
| Zoonotic potential of animal prion disease | Jones et al. (2009) | BSE, scrapie | Brain homogenate from transgenic mice expressing human PrP | First PMCA study to show the conversion susceptibility of human PrP to BSE but not scrapie prions |
| Barria et al. (2011) | CWD | Brain homogenate from transgenic mice expressing human PrP | CWD, after either in vivo passages in animals or in vitro passages by PMCA, is able to convert human PrPC to PrPSc, indicating the potential of CWD prions to infect humans | |
| Wang et al. (2021) | CWD | Non-CJD human brain homogenate | CWD-seeded, PMCA-amplified human PrPSc is able to induce bona fide prion disease in humanized transgenic mice, demonstrating the ability of CWD prions to cross the species barrier and infect humans | |
| Pritzkow (2022) | North American CWD and Norwegian CWD prions | Brain homogenate from transgenic mice expressing human PrP | Cross-species PMCA results indicate North American CWD prions have more zoonotic potential than Norwegian CWD prions |