{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T12:09:20Z","timestamp":1778328560258,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Protein misfolding is linked to many neurodegenerative diseases. In some cases, misfolding can propagate through a prion\u2010like mechanism whereby natively folded molecules are converted into more copies of the misfolded isoform. Prion\u2010like propagation of misfolding is an attractive therapeutic target, but difficulties with assaying conversion directly and simply have severely limited efforts to find drugs targeting conversion of disease\u2010related proteins. Here, we demonstrate a scalable enzymatic assay for testing potential inhibitors of prion\u2010like conversion in superoxide dismutase\u20101 (SOD1), whose misfolding is linked to amyotrophic lateral sclerosis (ALS). We tested several small\u2010molecule inhibitors of SOD1 aggregation to determine if they also inhibited prion\u2010like conversion. We found that some compounds, like telbivudine and cisplatin, did indeed significantly delay conversion, but others, like baicalein and quercetin, had little effect. Surprisingly, some compounds, like two statins tested, actually accelerated conversion, suggesting that they might act to promote ALS progression. These results underline the fact that conversion and aggregation are distinct biophysical processes. The ability of the assay to identify compounds effective at delaying prion\u2010like conversion holds out promise for applications in future drug discovery efforts that target propagated misfolding specifically.<\/jats:p>","DOI":"10.1002\/pro.70535","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:46:41Z","timestamp":1774273601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Scalable assay to identify inhibitors of prion\u2010like propagation of protein misfolding as potential therapeutics for neurodegeneration"],"prefix":"10.1002","volume":"35","author":[{"given":"Abhishek","family":"Narayan","sequence":"first","affiliation":[{"name":"Department of Physics University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Neupane","sequence":"additional","affiliation":[{"name":"Department of Physics University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4695-0397","authenticated-orcid":false,"given":"Michael T.","family":"Woodside","sequence":"additional","affiliation":[{"name":"Department of Physics University of Alberta  Edmonton Alberta Canada"},{"name":"Centre for Prions and Protein Folding Diseases University of Alberta  Edmonton Alberta Canada"},{"name":"Li Ka Shing Institute of Virology University of Alberta  Edmonton Alberta 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