{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T10:40:10Z","timestamp":1763116810006,"version":"3.45.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK029023"],"award-info":[{"award-number":["DK029023"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Small Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    Accumulation of huntingtin exon\u20101 protein (htt\n                    <jats:sup>ex1<\/jats:sup>\n                    ) fibrils within neurons occurs when the polyglutamine region exceeds \u224835 residues and is responsible for Huntington disease, a fatal neurodegenerative condition. Recent work has shown that selenium nanoparticles (SeNP) are protective against neurodegeneration. Herein, the mechanistic basis for SeNP modulation of htt\n                    <jats:sup>ex1<\/jats:sup>\n                    aggregation is explored. Fibril formation of htt\n                    <jats:sup>ex1<\/jats:sup>\n                    entails two distinct processes on timescales differing by many orders of magnitude: prenucleation oligomerization on the microsecond timescale to generate a low population of transient tetramers that undergo slow (hours timescale) unimolecular conversion into elongation\u2010competent nuclei, followed by elongation and secondary nucleation. Using NMR spectroscopy, fluorescence immunostaining, and transmission electron microscopy, the interaction of SeNPs with two htt\n                    <jats:sup>ex1<\/jats:sup>\n                    protein constructs, htt\n                    <jats:sup>ex1<\/jats:sup>\n                    Q\n                    <jats:sub>7<\/jats:sub>\n                    and htt\n                    <jats:sup>ex1<\/jats:sup>\n                    Q\n                    <jats:sub>35<\/jats:sub>\n                    containing 7 and 35 glutamine repeats, respectively, is studied. htt\n                    <jats:sup>ex1<\/jats:sup>\n                    Q\n                    <jats:sub>7<\/jats:sub>\n                    undergoes transient prenucleation tetramerization but remains largely monomeric over a period of weeks, while htt\n                    <jats:sup>ex1<\/jats:sup>\n                    Q\n                    <jats:sub>35<\/jats:sub>\n                    forms fibrils within a period of hours. It is shown that SeNPs reduce the rate of fibril formation substoichiometrically with respect to monomer by selectively targeting and binding with nanomolar affinity to the extendable ends of elongation\u2010competent species of htt\n                    <jats:sup>ex1<\/jats:sup>\n                    Q\n                    <jats:sub>35<\/jats:sub>\n                    , thereby reducing the pool of free extendable ends.\n                  <\/jats:p>","DOI":"10.1002\/smsc.202500345","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T09:09:51Z","timestamp":1757754591000},"source":"Crossref","is-referenced-by-count":0,"title":["Kinetic Mechanism of Substoichiometric Inhibition of Huntingtin Exon\u20101 Protein Aggregation by Selenium Nanoparticles"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9768-403X","authenticated-orcid":false,"given":"Francesco","family":"Torricella","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Physics National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda MD 20892\u20100520 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitali","family":"Tugarinov","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda MD 20892\u20100520 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-1027","authenticated-orcid":false,"given":"G. Marius","family":"Clore","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda MD 20892\u20100520 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2006.00335.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4604"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500335w"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00450"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.02.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja110715f"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b00281"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521933113"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15462"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.353839"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02360-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.06.021"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c00509"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55062-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.12.010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320626110"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18065"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.813667"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821216116"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.0c01636"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922264117"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2207690119"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202309217"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.4c01410"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c05571"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202100055"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b11441"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.020"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.604"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.004621"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167222"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2305823120"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.9b12319"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano14020160"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c05011"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsanm.3c02749"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.06.035"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2025.169269"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10577"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583514000122"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnmrs.2021.10.001"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.4c02509"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00599-8"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b02619"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c03032"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsanm.3c06292"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S193886"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2253"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-005-4425-x"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00197809"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1744152"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1137\/S1064827594276424"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja051306e"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