{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:30:24Z","timestamp":1791318624403,"version":"4.3.1"},"reference-count":62,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":1492,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b1\u2010Synuclein filaments are the major component of intracytoplasmic inclusion bodies characteristic of Parkinson's disease and related disorders. The process of \u03b1\u2010synuclein filament formation proceeds via intermediate or protofibrillar species, each of which may be cytotoxic. Because high levels of calcium(II) and other metal ions may play a role in disease pathogenesis, we investigated the influence of calcium and other metals on \u03b1\u2010synuclein speciation. Here we report that calcium(II) and cobalt(II) selectively induce the rapid formation of discrete annular \u03b1\u2010synuclein oligomeric species. We used atomic force microscopy to monitor the aggregation state of \u03b1\u2010synuclein after 1 d at 4\u00b0C in the presence of a range of metal ions compared with the filament formation pathway in the absence of metal ions. Three classes of effect were observed with different groups of metal ions: (1) Copper(II), iron(III), and nickel(II) yielded 0.8\u20134 nm spherical particles, similar to \u03b1\u2010synuclein incubated without metal ions; (2) magnesium(II), cadmium(II), and zinc(II) gave larger, 5\u20138 nm spherical oligomers; and, (3) cobalt(II) and calcium(II) gave frequent annular oligomers, 70\u201390 nm in diameter with calcium(II) and 22\u201330 nm in diameter with cobalt(II). In the absence of metal ions, annular oligomers ranging 45\u201390 nm in diameter were observed after 10 d incubation, short branched structures appeared after a further 3 wk and extended filaments after 2\u20133 mo. Previous studies have shown that \u03b1\u2010synuclein calcium binding is mediated by the acidic C terminus. We found that truncated \u03b1\u2010synuclein (1\u2013125), lacking the C\u2010terminal 15 amino acids, did not form annular oligomers upon calcium addition, indicating the involvement of the calcium\u2010binding domain.<\/jats:p>","DOI":"10.1110\/ps.04879704","type":"journal-article","created":{"date-parts":[[2004,11,10]],"date-time":"2004-11-10T20:26:26Z","timestamp":1100118386000},"page":"3245-3252","source":"Crossref","is-referenced-by-count":150,"title":["Calcium(II) selectively induces \u03b1\u2010synuclein annular oligomers via interaction with the C\u2010terminal domain"],"prefix":"10.1002","volume":"13","author":[{"given":"Rachel","family":"Lowe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean L.","family":"Pountney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poul Henning","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Ping","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas H.","family":"Voelcker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10637"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067389"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-002-1301-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/416507a"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-20-08797.2002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00021.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01213-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi991447r"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.571"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-10-04081.2003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01440-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi020139h"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4538"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00004-9"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1098\/rstb.1999.0466","article-title":"Filamentous nerve cell inclusions in neurodegenerative diseases: Tauopathies and \u03b1\u2010synucleinopathies","volume":"354","author":"Goedert M.","year":"1999","journal-title":"Philos. 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