{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:20:20Z","timestamp":1789651220905,"version":"4.0.0"},"reference-count":87,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inherited mutations in the Prion protein (PrP), encoded by the PRNP gene, have been associated with autosomal dominant neurodegenerative disorders, such as Creutzfeldt\u2013Jacob disease (CJD), Gerstmann\u2013Str\u00e4ussler\u2013Scheinker syndrome (GSS), and Fatal Familial Insomnia (FFI). Notably, PRNP mutations have also been described in clinical pictures resembling other neurodegenerative diseases, such as frontotemporal dementia. Regarding the pathogenesis, it has been observed that these point mutations are located in the C-terminal region of the PRNP gene and, currently, the potential significance of the N-terminal domain has largely been underestimated. The purpose of this report is to review and provide current insights into the pathogenic mechanisms of PRNP mutations, emphasizing the differences between the C- and N-terminal regions and focusing, in particular, on the lesser-known flexible N-terminal, for which recent biophysical evidence has revealed a physical interaction with the globular C-terminal domain of the cellular prion protein (PrPC).<\/jats:p>","DOI":"10.3390\/ijms20143606","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T10:44:51Z","timestamp":1563878691000},"page":"3606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Mutations in Prion Protein Gene: Pathogenic Mechanisms in C-Terminal vs. N-Terminal Domain, a Review"],"prefix":"10.3390","volume":"20","author":[{"given":"Livia","family":"Bernardi","sequence":"first","affiliation":[{"name":"Regional Neurogenetic Centre, ASP Catanzaro, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia C.","family":"Bruni","sequence":"additional","affiliation":[{"name":"Regional Neurogenetic Centre, ASP Catanzaro, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/bpa.12695","article-title":"Recent advances in the histo-molecular pathology of human prion disease","volume":"29","author":"Baiardi","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0092-8674(00)81163-0","article-title":"Prion protein biology","volume":"93","author":"Prusiner","year":"1998","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/B978-0-12-802395-2.00028-6","article-title":"Prion diseases","volume":"145","author":"Ironside","year":"2017","journal-title":"Handb. 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