{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:50:22Z","timestamp":1789422622191,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,12,20]],"date-time":"2001-12-20T00:00:00Z","timestamp":1008806400000},"content-version":"vor","delay-in-days":96,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2001,9,15]]},"abstract":"<jats:p>Human prion diseases are characterized by the conversion of the normal prion protein (PrP<jats:sup>C<\/jats:sup>) into a pathogenic isomer (PrP<jats:sup>Sc<\/jats:sup>). Distinct PrP<jats:sup>Sc<\/jats:sup> conformers are associated with different subtypes of prion diseases. PrP<jats:sup>C<\/jats:sup> binds copper and has antioxidation activity. Changes in metal\u2010ion occupancy can lead to significant decline of the antioxidation activity and changes in conformation of the protein. We studied the trace element status of brains from patients with sporadic Creutzfeldt\u2013Jakob disease (sCJD). We found a decrease of up to 50% of copper and an increase in manganese of approximately 10\u2010fold in the brain tissues from sCJD subjects. We have also studied the metal occupancy of PrP in sCJD patients. We observed striking elevation of manganese and, to a lesser extent, of zinc accompanied by significant reduction of copper bound to purified PrP in all sCJD variants, determined by the PrP genotype and PrP<jats:sup>Sc<\/jats:sup> type, combined. Both zinc and manganese were undetectable in PrP<jats:sup>C<\/jats:sup> preparations from controls. Copper and manganese changes were pronounced in sCJD subjects homozygous for methionine at codon\u2003129 and carrying PrP<jats:sup>Sc<\/jats:sup> type\u20101. Anti\u2010oxidation activity of purified PrP was dramatically reduced by up to 85% in the sCJD variants, and correlated with increased in oxidative stress markers in sCJD brains. These results suggest that altered metal\u2010ion occupancy of PrP plays a pivotal role in the pathogenesis of prion diseases. Since the metal changes differed in each sCJD variants, they may contribute to the diversity of PrP<jats:sup>Sc<\/jats:sup> and disease phenotype in\u00a0sCJD. Finally, this study also presented two potential approaches in the diagnosis of CJD; the significant increase in brain manganese makes it potentially detectable by MRI, and the binding of manganese by PrP in sCJD might represent a novel diagnostic marker.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2001.00522.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:56:36Z","timestamp":1047452196000},"page":"1400-1408","source":"Crossref","is-referenced-by-count":159,"title":["Aberrant metal binding by prion protein in human prion disease"],"prefix":"10.1111","volume":"78","author":[{"given":"Boon\u2010Seng","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu G.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Colucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruliang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gambetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Sun","family":"Sy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac970783f"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.01009.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3440001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/37783"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.6.1180"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00009.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(99)00073-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(01)00249-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/77476"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75718-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.519"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)00203-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1439789"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0290"},{"key":"e_1_2_7_16_1","volume-title":"Free Radicals in Biology and Medicine","author":"Halliwell B.","year":"1999"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5298.402"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3986"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.23.6855"},{"key":"e_1_2_7_20_1","first-page":"49","article-title":"Brain manganese concentrations in human aging and Alzheimer's disease","volume":"5","author":"Markesbery W. R.","year":"1984","journal-title":"Neurotoxicology"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2839"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/386232a0"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199908)46:2<224::aid-ana12>3.3.co;2-n"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.18.10168"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20025"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5295.2079"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/9030"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.9.2.332"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2911"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3604"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00028.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8812"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1471-4159.2001.00522.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1471-4159.2001.00522.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T15:52:03Z","timestamp":1697644323000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1471-4159.2001.00522.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,15]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,9,15]]}},"alternative-id":["10.1046\/j.1471-4159.2001.00522.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1471-4159.2001.00522.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,15]]}}}