{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:54:24Z","timestamp":1791942864662,"version":"4.3.4"},"reference-count":33,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T00:00:00Z","timestamp":1514419200000},"content-version":"vor","delay-in-days":1081,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100003404","name":"Foundation for Fundamental Research on Matter","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100003404","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"NanoNextNL","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The formation of amyloid fibrils of \u03b1-synuclein (\u03b1Syn), the key protein in Parkinson\u2019s disease, is an autocatalytic process that is seeded by mature \u03b1Syn fibrils. Based on systematic measurements of the dependence of the fibril growth rate on the concentrations of monomers and preformed fibrillar seeds, we propose a mechanism of \u03b1Syn aggregation that includes monomer binding to fibril ends and secondary nucleation by fibril breaking. The model explains the increase of the \u03b1Syn aggregation rate under shaking conditions and the exponential increase in the fraction of fibrillar protein at the initial stages of \u03b1Syn aggregation. The proposed autocatalytic mechanism also accounts for the high variability in the aggregation lag time. The rate constant of monomer binding to the ends of fibrils, k+ \u2248 1.3 mM\u20131 s\u20131, was estimated from the aggregation rate and previously reported average fibril lengths. From the aggregation rates at low concentrations the binding of monomeric \u03b1Syn to fibrils was found to be almost irreversible, with an equilibrium dissociation constant (Kd) smaller than 3 \u03bcM.<\/jats:p>","DOI":"10.1021\/jp5111604","type":"journal-article","created":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T22:07:26Z","timestamp":1421100446000},"page":"1912-1918","source":"Crossref","is-referenced-by-count":47,"title":["Fibril\nBreaking Accelerates \u03b1-Synuclein\nFibrillization"],"prefix":"10.1021","volume":"119","author":[{"given":"Volodymyr V.","family":"Shvadchak","sequence":"first","affiliation":[{"name":"FOM Institute AMOLF , Science Park 104 , ,","place":["Amsterdam, The Netherlands, 1098 XG"]},{"name":"University of Twente , , P. O. Box 217, ,","place":["Enschede, The Netherlands, 7500 AE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille M. A. E.","family":"Claessens","sequence":"additional","affiliation":[{"name":"University of Twente , , P. O. Box 217, ,","place":["Enschede, The Netherlands, 7500 AE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"FOM Institute AMOLF , Science Park 104 , ,","place":["Amsterdam, The Netherlands, 1098 XG"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2015,1,12]]},"reference":[{"key":"2026090219013893000_cit1","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.neuron.2013.09.004","article-title":"The function of \u03b1-synuclein","volume":"79","author":"Bendor","year":"2013","journal-title":"Neuron"},{"key":"2026090219013893000_cit2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0896-6273(95)90302-X","article-title":"The precursor protein\nof non-A\u03b2 component of Alzheimer\u2019s disease amyloid is\na presynaptic protein of the central nervous system","volume":"14","author":"Iwai","year":"1995","journal-title":"Neuron"},{"key":"2026090219013893000_cit3","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.1523\/JNEUROSCI.1594-04.2004","article-title":"Lipid rafts mediate the synaptic localization of \u03b1-synuclein","volume":"24","author":"Fortin","year":"2004","journal-title":"J. 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