{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:03:30Z","timestamp":1782281010463,"version":"3.54.5"},"posted":{"date-parts":[[2025,10,3]]},"group-title":"Biochemistry","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"United States Nuclear Regulatory Commission","award":["31310018M0012"],"award-info":[{"award-number":["31310018M0012"]}]},{"name":"NIH NIA T32","award":["AG000266"],"award-info":[{"award-number":["AG000266"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,3]]},"abstract":"<jats:p>\n                  Parkinson's disease (PD) is a prevalent age-related neurodegenerative syndrome, partially thought to be caused by a decrease in alpha-synuclein proteostasis. Anle138b = 5-(1,3-benzodioxol-5-yl)-3-(3-bromophenyl)-1H-pyrazole (\n                  <jats:bold>HL<\/jats:bold>\n                  ), is undergoing clinical trials as a promising mitigator of alpha-synuclein aggregation. Because complexation to metals is known to modulate the activity of several drugs, we have prepared and characterized:\n                  <jats:bold>\n                    H\n                    <jats:sub>2<\/jats:sub>\n                    L(ClO\n                    <jats:sub>4<\/jats:sub>\n                    )\n                  <\/jats:bold>\n                  ,\n                  <jats:bold>\n                    [CuI(\u03bc-L)]\n                    <jats:sub>3<\/jats:sub>\n                  <\/jats:bold>\n                  , and\n                  <jats:bold>\n                    [AgI(\u03bc-L)]\n                    <jats:sub>3<\/jats:sub>\n                  <\/jats:bold>\n                  . To better understand the bioviability of these compounds, we monitored their effects in a cell culture model of alpha-synuclein protein aggregation using human alpha-synuclein pre-formed fibrils (PFFs). Using two different anti-alpha-synuclein antibodies, our data suggests that\n                  <jats:bold>\n                    [AgI(\u03bc-L)]\n                    <jats:sub>3<\/jats:sub>\n                  <\/jats:bold>\n                  decreases a C-terminal truncated protein that is approximately 12.4 kDa, as well as increases the size and alters the shape of PFF-induced aggregates. This indicates that\n                  <jats:bold>\n                    [AgI(\u03bc-L)]\n                    <jats:sub>3<\/jats:sub>\n                  <\/jats:bold>\n                  impacts aggregation in a manner different from\n                  <jats:bold>HL<\/jats:bold>\n                  and may serve as a novel tool for studying C-terminal truncation related aggregation chemistry.\n                <\/jats:p>","DOI":"10.1101\/2025.10.01.679869","type":"posted-content","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T21:55:10Z","timestamp":1759528510000},"source":"Crossref","is-referenced-by-count":0,"title":["Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size"],"prefix":"10.64898","author":[{"given":"Kelly L","family":"Rue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Chun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indranil","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Tachiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josue","family":"Ballesteros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie K.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J.","family":"Lithgow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wisam A.","family":"Al Isawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gellert","family":"Mezei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna Yakov","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael G.","family":"Raptis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.01.679869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:13:39Z","timestamp":1782278019000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.01.679869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.10.01.679869","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1002\/cmdc.202500890","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,10,3]]},"subtype":"preprint"}}