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Compelling evidence indicates that prevention and\/or reduction of PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    replication are promising therapeutic strategies against prion diseases. However, the existence of different PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    conformations (or strains) associated with disease represents a major problem when identifying anti\u2010prion compounds. Efforts to identify strain\u2010specific anti\u2010prion molecules are limited by the lack of biologically relevant high\u2010throughput screening platforms to interrogate compound libraries. Here, we describe adaptations to the protein misfolding cyclic amplification (PMCA) technology (able to faithfully replicate PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    strains) that increase its throughput to facilitate the screening of anti\u2010prion molecules. The optimized PMCA platform includes a reduction in sample and reagents, as well as incubation\/sonication cycles required to efficiently replicate and detect rodent\u2010adapted and cervid PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    strains. The visualization of PMCA products was performed via dot blots, a method that contributed to reduced processing times. These technical changes allowed us to evaluate small molecules with previously reported anti\u2010prion activity. This proof\u2010of\u2010principle screening was evaluated for six rodent\u2010adapted prion strains. Our data show that these compounds targeted either none, all or some PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    strains at variable concentrations, demonstrating that this PMCA system is suitable to test compound libraries for putative anti\u2010prion molecules targeting specific PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    strains. Further analyses of a small compound library against deer prions demonstrate the potential of this new PMCA format to identify strain\u2010specific anti\u2010prion molecules. The data presented here demonstrate the use of the PMCA technique in the selection of prion strain\u2010specific anti\u2010prion compounds.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400614r","type":"journal-article","created":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T05:39:52Z","timestamp":1722145192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adaptation of the protein misfolding cyclic amplification (PMCA) technique for the screening of anti\u2010prion compounds"],"prefix":"10.1096","volume":"38","author":[{"given":"Katherine","family":"Do","sequence":"first","affiliation":[{"name":"Department of Neurology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0271-9674","authenticated-orcid":false,"given":"Rebeca","family":"Benavente","sequence":"additional","affiliation":[{"name":"Department of Neurology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-6310","authenticated-orcid":false,"given":"Celso S. 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