{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:13:10Z","timestamp":1788415990538,"version":"build-2803163510"},"reference-count":185,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Prion diseases are rare, transmissible, and invariably fatal neurodegenerative disorders caused by the conformational conversion of cellular prion protein (PrP\n                      <jats:sup>C<\/jats:sup>\n                      ) into its pathogenic isoform (PrP\n                      <jats:sup>Sc<\/jats:sup>\n                      ). Despite decades of research, no licensed disease-modifying therapies are currently available. This reflects the rapid clinical course of these disorders, the difficulty of early diagnosis, and the biological challenge of targeting a self-propagating protein misfolding process within the central nervous system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This narrative scoping review maps the current therapeutic landscape in prion disease, with emphasis on the molecular mechanisms of pathogenesis, historical and emerging treatment strategies, and other exploratory therapeutic candidates. The included literature covers PrP-lowering strategies, anti-PrP immunotherapy, downstream modulation of glial dysfunction, and broader translational barriers that continue to limit clinical development. Overall, therapeutic research has shifted from repurposed small molecules toward more mechanism-based strategies. These include\n                      <jats:italic>PRNP<\/jats:italic>\n                      -targeting strategies using antisense oligonucleotides, siRNA, and genomic editing technologies, as well as anti-PrP immunotherapy. Collectively, these strategies provide a stronger biological rationale than earlier compounds, although evidence from human trials remains limited, early-phase, or absent. In parallel, increasing evidence indicates that maladaptive glial cell activation and chronic neuroinflammation contribute substantially to disease progression and may represent additional therapeutic targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current evidence supports increasing emphasis on integrated, mechanism-based strategies that combine suppression of prion propagation with modulation of downstream tissue injury. However, evidence of clinical efficacy in human patients is lacking. Future progress will depend on earlier diagnosis, improved translational models, and more rigorous human evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1924347","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:21:00Z","timestamp":1788412860000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic strategies in prion disease: current evidence, translational challenges, and emerging directions"],"prefix":"10.3389","volume":"20","author":[{"given":"Yixin","family":"Zhu","sequence":"first","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush","place":["Midlothian, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry M.","family":"Bradford","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush","place":["Midlothian, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Mabbott","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush","place":["Midlothian, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.11599\/germs.2015.1075","article-title":"Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz","volume":"5","author":"Abah","year":"2015","journal-title":"Germs"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"639008","DOI":"10.3389\/fimmu.2021.639008","article-title":"Cross-linking cellular prion protein induces neuronal type 2-like hypersensitivity","volume":"12","author":"Adhikari","year":"2021","journal-title":"Front. 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