{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:50:49Z","timestamp":1788612649312,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T00:00:00Z","timestamp":1629590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["#Me928\/19"],"award-info":[{"award-number":["#Me928\/19"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Investissements d'avenir","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"]}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/14207-7"],"award-info":[{"award-number":["2017\/14207-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or \u03b1-synuclein amyloid aggregates (\u03b1Sa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or \u03b1Sa stimulation, COL-3 (10, 20 \u00b5M) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-\u03b1. COL-3\u2032s inhibitory effects on TNF-\u03b1 were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 \u00b5M), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-\u03b1 release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner.<\/jats:p>","DOI":"10.3390\/cells10082163","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:42:12Z","timestamp":1629668532000},"page":"2163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress"],"prefix":"10.3390","volume":"10","author":[{"given":"Nilson Carlos","family":"Ferreira Junior","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute-ICM, Inserm, CNRS, APHP, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"},{"name":"Department of Basic and Oral Biology, FORP, Campus USP, University of S\u00e3o Paulo, Av. Caf\u00e9, s\/no, Ribeir\u00e3o Preto 14040-904, Brazil"},{"name":"USP, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), S\u00e3o Paulo 05508-220, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-7379","authenticated-orcid":false,"given":"Maur\u00edcio","family":"dos Santos Pereira","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute-ICM, Inserm, CNRS, APHP, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"},{"name":"Department of Basic and Oral Biology, FORP, Campus USP, University of S\u00e3o Paulo, Av. Caf\u00e9, s\/no, Ribeir\u00e3o Preto 14040-904, Brazil"},{"name":"USP, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), S\u00e3o Paulo 05508-220, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Francis","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute-ICM, Inserm, CNRS, APHP, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute-ICM, Inserm, CNRS, APHP, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Martorell","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute-ICM, Inserm, CNRS, APHP, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Gonz\u00e1lez-Lizarraga","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), CP 4000 Tucum\u00e1n, Argentina"}],"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"}]},{"given":"Rosana","family":"Chehin","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), CP 4000 Tucum\u00e1n, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Del Bel","sequence":"additional","affiliation":[{"name":"Department of Basic and Oral Biology, FORP, Campus USP, University of S\u00e3o Paulo, Av. 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