{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:48:29Z","timestamp":1776098909397,"version":"3.50.1"},"reference-count":147,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Prion diseases represent a group of rare, progressive, and invariably fatal neurodegenerative disorders. Their hallmark is the infectious nature of the misfolded prion protein (PrP^Sc), which propagates by inducing conformational changes in the physiological form (PrP^C). Despite advances in basic science, these disorders still pose major clinical and therapeutic challenges. Methods: A narrative review of the scientific literature was conducted across major biomedical databases, including PubMed, Scopus, Web of Science, and Google Scholar, covering publications up to January 2025. In addition, we describe an illustrative clinical case of a young patient with probable iatrogenic Creutzfeldt\u2013Jakob disease following corneal transplantation, used to highlight diagnostic uncertainty and infection-control implications. Findings: Evidence confirms that PrP^Sc drives neurodegenerative processes and transmissibility, with phenotypic and genetic variants influencing clinical course and prognosis. From a diagnostic perspective, neuroimaging techniques and cerebrospinal fluid biomarkers have undergone substantial refinement, with RT-QuIC emerging as a highly specific and sensitive assay. Therapeutic options remain unsatisfactory: no treatment has shown a significant impact on survival. However, innovative strategies (including monoclonal antibodies, gene-based interventions, and modulation of PrP^C) represent promising avenues of investigation. Conclusions: Prion diseases remain an unresolved challenge at the intersection of neurology and infectious diseases. Earlier diagnosis through advanced biomarkers and continued development of targeted therapies are essential to improve patient management, while the persistence of iatrogenic cases underscores the ongoing relevance of surveillance and preventive strategies in clinical practice.<\/jats:p>","DOI":"10.3390\/v18020216","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Prion Disease: Pathogenesis, Diagnosis and Public Health"],"prefix":"10.3390","volume":"18","author":[{"given":"Paola","family":"Bellini","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4045-5774","authenticated-orcid":false,"given":"Francesco","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, 6903 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Neuroradiology, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, 6903 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo W.","family":"Cereda","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, 6903 Lugano, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana (USI), 6962 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, 6903 Lugano, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana (USI), 6962 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Bianco","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, 6903 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2999-3707","authenticated-orcid":false,"given":"Marco","family":"Bongiovanni","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana (USI), 6962 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel Proteinaceous Infectious Particles Cause Scrapie","volume":"216","author":"Prusiner","year":"1982","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1126\/science.1675487","article-title":"Molecular Biology of Prion Diseases","volume":"252","author":"Prusiner","year":"1991","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.neuro.24.1.519","article-title":"Prion Diseases of Humans and Animals: Their Causes and Molecular Basis","volume":"24","author":"Collinge","year":"2001","journal-title":"Annu. 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