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Review
. 2020:175:77-119.
doi: 10.1016/bs.pmbts.2020.07.001. Epub 2020 Aug 28.

The role of prion strain diversity in the development of successful therapeutic treatments

Sara A M Holec  1 , Alyssa J Block  2 , Jason C Bartz  3
Affiliations
Review

The role of prion strain diversity in the development of successful therapeutic treatments

Sara A M Holec et al. Prog Mol Biol Transl Sci. 2020.

Abstract

Prions are a self-propagating misfolded conformation of a cellular protein. Prions are found in several eukaryotic organisms with mammalian prion diseases encompassing a wide range of disorders. The first recognized prion disease, the transmissible spongiform encephalopathies (TSEs), affect several species including humans. Alzheimer's disease, synucleinopathies, and tauopathies share a similar mechanism of self-propagation of the prion form of the disease-specific protein reminiscent of the infection process of TSEs. Strain diversity in prion disease is characterized by differences in the phenotype of disease that is hypothesized to be encoded by strain-specific conformations of the prion form of the disease-specific protein. Prion therapeutics that target the prion form of the disease-specific protein can lead to the emergence of drug-resistant strains of prions, consistent with the hypothesis that prion strains exist as a dynamic mixture of a dominant strain in combination with minor substrains. To overcome this obstacle, therapies that reduce or eliminate the template of conversion are efficacious, may reverse neuropathology, and do not result in the emergence of drug resistance. Recent advancements in preclinical diagnosis of prion infection may allow for a combinational approach that treats the prion form and the precursor protein to effectively treat prion diseases.

Keywords: Anti-prion therapy; Prion disease; Prion strains.

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Figures

Fig. 1
Fig. 1
Mechanistic location of therapeutic targets for PrP prion diseases. Therapeutic targets: ❶ PrPC post-translational processing, metabolism, cellular trafficking, or localization; ❷ PrPC by binding or inducing conformational change that prevents PrPC interaction; ❸ PrPSc by stabilization, redistribution; ❹ conversion process by blocking binding site on PrPC, capping growth, inhibition of cofactor interactions, or ❺ promoting fragmentation or ❻ clearance from the host.
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References

    1. Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982;216 (4542):136–144. - PubMed
    1. Horiuchi M, Caughey B. Specific binding of normal prion protein to the scrapie form via a localized domain initiates its conversion to the protease-resistant state. EMBO J. 1999;18(12):3193–3203. - PMC - PubMed
    1. Bessen RA, Kocisko DA, Raymond GJ, Nandan S, Lansbury PT, Caughey B. Non-genetic propagation of strain-specific properties of scrapie prion protein. Nature. 1995;375(6533):698–700. - PubMed
    1. Kocisko DA, Come JH, Priola SA, et al. Cell-free formation of protease-resistant prion protein. Nature. 1994;370(6489):471–474. - PubMed
    1. Du Z, Park KW, Yu H, Fan Q, Li L. Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae. Nat Genet. 2008;40(4):460–465. - PMC - PubMed

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