{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:24:07Z","timestamp":1792160647991,"version":"4.4.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"32","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,8]]},"abstract":"<jats:p>\n                    Rapid neurodegeneration distinguishes prion disease from other neurodegenerative disorders. Notably, normal prion protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ) is essential for prion-induced rapid neurodegeneration, but the underlying mechanism remains unknown. Here, we show that the unstructured N-terminal region of PrP\n                    <jats:sup>C<\/jats:sup>\n                    induces rapid and lethal neurodegeneration in mice, accompanied by the hallmark of prion disease, spongiosis. The neurotoxic N-terminal PrP is soluble, associates peripherally with lipid membranes, and induces neurotoxicity only when a critical threshold is exceeded. Both the N-terminally localized KKRPKP sequence and octarepeats contribute to neurotoxicity, with KKRPKP being essential. Without it, the N-terminal PrP is innocuous but exacerbates either neurodegeneration caused by N-terminal PrP or neurodegeneration in prion disease induced by intracerebral prion inoculation in mice. Our findings establish that soluble N-terminal PrP causes rapid neurodegeneration in prion disease and is a target for intervention.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw6867","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:58:27Z","timestamp":1754503107000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Soluble N-terminal region of prion protein causes rapid neurodegeneration in prion disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4120-179X","authenticated-orcid":true,"given":"Runchuan","family":"Yan","sequence":"first","affiliation":[{"name":"College of Biological Sciences, China Agricultural University, Beijing 100193, China."},{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6451-2173","authenticated-orcid":true,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biological Sciences, China Agricultural University, Beijing 100193, China."},{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7524-8973","authenticated-orcid":true,"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."},{"name":"School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7017-7472","authenticated-orcid":true,"given":"Xiangyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Han","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Huang","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China."},{"name":"School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-9864","authenticated-orcid":true,"given":"Qi","family":"Shi","sequence":"additional","affiliation":[{"name":"National key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Dong","sequence":"additional","affiliation":[{"name":"National key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-0370","authenticated-orcid":true,"given":"Wen-Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Jiangxi Academy of Clinical Medical Sciences, Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 33022, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-4161","authenticated-orcid":true,"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Biological Sciences, China Agricultural University, Beijing 100193, China."},{"name":"Chinese Institute for Brain Research, Beijing 102206, 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