{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:51:49Z","timestamp":1775494309736,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2016-0481"],"award-info":[{"award-number":["2016-0481"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione Sacchetti","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathological aggregation of amyloidogenic proteins is a hallmark of many neurological diseases, including Alzheimer\u2019s disease and prion diseases. We have shown both in vitro and in vivo that doxycycline can inhibit the aggregation of A\u03b242 amyloid fibrils and disassemble mature amyloid fibrils. However, the molecular mechanisms of the drug\u2019s anti-amyloidogenic property are not understood. In this study, a series of molecular dynamics simulations were performed to explain the molecular mechanism of the destabilization of A\u03b242 fibrils by doxycycline and to compare the action of doxycycline with those of iododoxorubicin (a toxic structural homolog of tetracyclines), curcumin (known to have anti-amyloidogenic activity) and gentamicin (an antibiotic with no experimental evidence of anti-amyloidogenic properties). We found that doxycycline tightly binds the exposed hydrophobic amino acids of the A\u03b242 amyloid fibrils, partly leading to destabilization of the fibrillar structure. Clarifying the molecular determinants of doxycycline binding to A\u03b242 may help devise further strategies for structure-based drug design for Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms20184641","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T03:40:06Z","timestamp":1568864406000},"page":"4641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The Anti-Amyloidogenic Action of Doxycycline: A Molecular Dynamics Study on the Interaction with A\u03b242"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-0130","authenticated-orcid":false,"given":"Alfonso","family":"Gautieri","sequence":"first","affiliation":[{"name":"Biomolecular Engineering Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-6704","authenticated-orcid":false,"given":"Marten","family":"Beeg","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1014-6225","authenticated-orcid":false,"given":"Marco","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Rigoldi","sequence":"additional","affiliation":[{"name":"Biomolecular Engineering Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Colombo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Salmona","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1182\/blood.V86.3.855.855","article-title":"New Drug Therapy of Amyloidoses: Resorption of AL-Type Deposits with 4\u2032-Iodo-4\u2032-Deoxydoxorubicin","volume":"86","author":"Gianni","year":"1995","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1073\/pnas.92.7.2959","article-title":"Interaction of the anthracycline 4\u2032-iodo-4\u2032-deoxydoxorubicin with amyloid fibrils: Inhibition of amyloidogenesis","volume":"92","author":"Merlini","year":"1995","journal-title":"Proc. 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