{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:26:19Z","timestamp":1793229979939,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2016-02364123"],"award-info":[{"award-number":["RF-2016-02364123"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 2019-2020"],"award-info":[{"award-number":["Ricerca Corrente 2019-2020"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2017483NH8_005"],"award-info":[{"award-number":["2017483NH8_005"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington disease (HD) is a devastating and presently untreatable neurodegenerative disease characterized by progressively disabling motor and mental manifestations. The sigma-1 receptor (\u03c31R) is a protein expressed in the central nervous system, whose 3D structure has been recently determined by X-ray crystallography and whose agonists have been shown to have neuroprotective activity in neurodegenerative diseases. To identify therapeutic agents against HD, we have implemented a drug repositioning strategy consisting of: (i) Prediction of the ability of the FDA-approved drugs publicly available through the ZINC database to interact with \u03c31R by virtual screening, followed by computational docking and visual examination of the 20 highest scoring drugs; and (ii) Assessment of the ability of the six drugs selected by computational analyses to directly bind purified \u03c31R in vitro by Surface Plasmon Resonance and improve the growth of fibroblasts obtained from HD patients, which is significantly impaired with respect to control cells. All six of the selected drugs proved able to directly bind purified \u03c31R in vitro and improve the growth of HD cells from both or one HD patient. These results support the validity of the drug repositioning procedure implemented herein for the identification of new therapeutic tools against HD.<\/jats:p>","DOI":"10.3390\/ijms22031293","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T09:03:45Z","timestamp":1611824625000},"page":"1293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Known Drugs Identified by Structure-Based Virtual Screening Are Able to Bind Sigma-1 Receptor and Increase Growth of Huntington Disease Patient-Derived Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8401-890X","authenticated-orcid":false,"given":"Theo","family":"Battista","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, 00185 Rome, Italy"},{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Pascarella","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, 00185 Rome, Italy"},{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0652-0974","authenticated-orcid":false,"given":"David Sasah","family":"Staid","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, 00185 Rome, Italy"},{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-0635","authenticated-orcid":false,"given":"Gianni","family":"Colotti","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-386X","authenticated-orcid":false,"given":"Jessica","family":"Rosati","sequence":"additional","affiliation":[{"name":"Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-8554","authenticated-orcid":false,"given":"Annarita","family":"Fiorillo","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, \u201cSapienza\u201d University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Casamassa","sequence":"additional","affiliation":[{"name":"Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"},{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Luigi","family":"Vescovi","sequence":"additional","affiliation":[{"name":"Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Giabbai","sequence":"additional","affiliation":[{"name":"Protein Facility, Structural Biology Lab, Elettra Sincrotrone Trieste, 34149 Basovizza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0642-3034","authenticated-orcid":false,"given":"Marta Stefania","family":"Semrau","sequence":"additional","affiliation":[{"name":"Protein Facility, Structural Biology Lab, Elettra Sincrotrone Trieste, 34149 Basovizza, Italy"},{"name":"Department of Cellular, Computational and Integrative Biology\u2014CIBIO, University of Trento, 38123 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5832-8381","authenticated-orcid":false,"given":"Sergio","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Huntington and Rare Diseases Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2590-3332","authenticated-orcid":false,"given":"Paola","family":"Storici","sequence":"additional","affiliation":[{"name":"Protein Facility, Structural Biology Lab, Elettra Sincrotrone Trieste, 34149 Basovizza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-1727","authenticated-orcid":false,"given":"Ferdinando","family":"Squitieri","sequence":"additional","affiliation":[{"name":"Huntington and Rare Diseases Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Morea","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7754-399X","authenticated-orcid":false,"given":"Andrea","family":"Ilari","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pharmthera.2009.07.001","article-title":"The pharmacology of sigma-1 receptors","volume":"124","author":"Maurice","year":"2009","journal-title":"Pharmacol. 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