{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:52:12Z","timestamp":1788612732727,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Association France Parkinson","award":["DOXYPARK; GAO2018"],"award-info":[{"award-number":["DOXYPARK; GAO2018"]}]},{"name":"Association France Parkinson","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"Association France Parkinson","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]},{"name":"Institut Carnot","award":["DOXYPARK; GAO2018"],"award-info":[{"award-number":["DOXYPARK; GAO2018"]}]},{"name":"Institut Carnot","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"Institut Carnot","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]},{"name":"Program Investissements d\u2019Avenir","award":["DOXYPARK; GAO2018"],"award-info":[{"award-number":["DOXYPARK; GAO2018"]}]},{"name":"Program Investissements d\u2019Avenir","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"Program Investissements d\u2019Avenir","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]},{"name":"Translational Research Infrastructure for Biotherapies in Neurosciences","award":["DOXYPARK; GAO2018"],"award-info":[{"award-number":["DOXYPARK; GAO2018"]}]},{"name":"Translational Research Infrastructure for Biotherapies in Neurosciences","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"Translational Research Infrastructure for Biotherapies in Neurosciences","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Several studies have reported that the tetracycline (TC) class antibiotic doxycycline (DOX) is effective against Parkinson\u2019s disease (PD) pathomechanisms. The aim of the present work was three-fold: (i) Establish a model system to better characterize neuroprotection by DOX; (ii) Compare the rescue effect of DOX to that of other TC antibiotics; (iii) Discover novel neuroprotective TCs having reduced antibiotic activity. For that, we used cultures of mouse midbrain dopamine (DA) neurons and experimental conditions that model iron-mediated oxidative damage, a key mechanism in PD pathobiology. We found that DOX and the other TC antibiotic, demeclocycline (DMC), provided sustained protection to DA neurons enduring iron-mediated insults, whereas chlortetracycline and non-TC class antibiotics did not. Most interestingly, non-antibiotic derivatives of DOX and DMC, i.e., DDOX and DDMC, respectively, were also robustly protective for DA neurons. Interestingly, DOX, DDOX, DMC, and DDMC remained protective for DA neurons until advanced stages of neurodegeneration, and the rescue effects of TCs were observable regardless of the degree of maturity of midbrain cultures. Live imaging studies with the fluorogenic probes DHR-123 and TMRM revealed that protective TCs operated by preventing intracellular oxidative stress and mitochondrial membrane depolarization, i.e., cellular perturbations occurring in this model system as the ultimate consequence of ferroptosis-mediated lipid peroxidation. If oxidative\/mitochondrial insults were generated acutely, DOX, DDOX, DMC, and DDMC were no longer neuroprotective, suggesting that these compounds are mostly effective when neuronal damage is chronic and of low-intensity. Overall, our data suggest that TC derivatives, particularly those lacking antibiotic activity, might be of potential therapeutic utility to combat low-level oxidative insults that develop chronically in the course of PD neurodegeneration.<\/jats:p>","DOI":"10.3390\/antiox12030575","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:52:21Z","timestamp":1677469941000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Rescue of Dopamine Neurons from Iron-Dependent Ferroptosis by Doxycycline and Demeclocycline and Their Non-Antibiotic Derivatives"],"prefix":"10.3390","volume":"12","author":[{"given":"Aurore","family":"Tourville","sequence":"first","affiliation":[{"name":"Paris Brain Institute\u2014ICM, Inserm, Sorbonne Universit\u00e9, CNRS, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7493-3646","authenticated-orcid":false,"given":"Sarah","family":"Viguier","sequence":"additional","affiliation":[{"name":"Paris Brain Institute\u2014ICM, Inserm, Sorbonne Universit\u00e9, CNRS, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Gonz\u00e1lez-Liz\u00e1rraga","sequence":"additional","affiliation":[{"name":"IMMCA, CONICET-UNT-SIPROSA, Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-6009","authenticated-orcid":false,"given":"Rodrigo Hern\u00e1n","family":"Tomas-Grau","sequence":"additional","affiliation":[{"name":"IMMCA, CONICET-UNT-SIPROSA, Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Paris Brain Institute\u2014ICM, Inserm, Sorbonne Universit\u00e9, CNRS, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-8980","authenticated-orcid":false,"given":"Jean-Michel","family":"Brunel","sequence":"additional","affiliation":[{"name":"UMR_MD1 Membranes et Cibles Th\u00e9rapeutiques, U1261 INSERM, Aix-Marseille Universit\u00e9, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Dos Santos Pereira","sequence":"additional","affiliation":[{"name":"Department of Basic and Oral Biology, USP, Ribeir\u00e3o Preto 14040-904, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Del-Bel","sequence":"additional","affiliation":[{"name":"Department of Basic and Oral Biology, USP, Ribeir\u00e3o Preto 14040-904, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosana","family":"Chehin","sequence":"additional","affiliation":[{"name":"IMMCA, CONICET-UNT-SIPROSA, Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Ferri\u00e9","sequence":"additional","affiliation":[{"name":"BioCIS, CNRS, Universit\u00e9 Paris-Saclay, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Raisman-Vozari","sequence":"additional","affiliation":[{"name":"Paris Brain Institute\u2014ICM, Inserm, Sorbonne Universit\u00e9, CNRS, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Figad\u00e8re","sequence":"additional","affiliation":[{"name":"BioCIS, CNRS, Universit\u00e9 Paris-Saclay, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5607-3119","authenticated-orcid":false,"given":"Patrick Pierre","family":"Michel","sequence":"additional","affiliation":[{"name":"Paris Brain Institute\u2014ICM, Inserm, Sorbonne Universit\u00e9, CNRS, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pneurobio.2013.04.004","article-title":"Mitochondrial Dysfunction and Oxidative Stress in Parkinson\u2019s 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