{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:35:52Z","timestamp":1785242152804,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T00:00:00Z","timestamp":1662249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["GAO 2018"],"award-info":[{"award-number":["GAO 2018"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["DOXYPARK"],"award-info":[{"award-number":["DOXYPARK"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PIP-CONICET 0183"],"award-info":[{"award-number":["PIP-CONICET 0183"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PIP-CONICET 11220130100619CO"],"award-info":[{"award-number":["PIP-CONICET 11220130100619CO"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PICT-MINCyT 2012\u20132882"],"award-info":[{"award-number":["PICT-MINCyT 2012\u20132882"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PIUNT-UNT D542\/1"],"award-info":[{"award-number":["PIUNT-UNT D542\/1"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PICT 2018-2989"],"award-info":[{"award-number":["PICT 2018-2989"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PICT 2018-3379"],"award-info":[{"award-number":["PICT 2018-3379"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PICT 2020-2255"],"award-info":[{"award-number":["PICT 2020-2255"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PIUNT 2020"],"award-info":[{"award-number":["PIUNT 2020"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["PIUNT D644\/1"],"award-info":[{"award-number":["PIUNT D644\/1"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["GAO 2018"],"award-info":[{"award-number":["GAO 2018"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["DOXYPARK"],"award-info":[{"award-number":["DOXYPARK"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PIP-CONICET 0183"],"award-info":[{"award-number":["PIP-CONICET 0183"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PIP-CONICET 11220130100619CO"],"award-info":[{"award-number":["PIP-CONICET 11220130100619CO"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PICT-MINCyT 2012\u20132882"],"award-info":[{"award-number":["PICT-MINCyT 2012\u20132882"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PIUNT-UNT D542\/1"],"award-info":[{"award-number":["PIUNT-UNT D542\/1"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PICT 2018-2989"],"award-info":[{"award-number":["PICT 2018-2989"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PICT 2018-3379"],"award-info":[{"award-number":["PICT 2018-3379"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PICT 2020-2255"],"award-info":[{"award-number":["PICT 2020-2255"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PIUNT 2020"],"award-info":[{"award-number":["PIUNT 2020"]}]},{"name":"Scientific and Technological Promotion National Agency\u2014Argentina","award":["PIUNT D644\/1"],"award-info":[{"award-number":["PIUNT D644\/1"]}]},{"name":"Tucum\u00e1n National University","award":["GAO 2018"],"award-info":[{"award-number":["GAO 2018"]}]},{"name":"Tucum\u00e1n National University","award":["DOXYPARK"],"award-info":[{"award-number":["DOXYPARK"]}]},{"name":"Tucum\u00e1n National University","award":["PIP-CONICET 0183"],"award-info":[{"award-number":["PIP-CONICET 0183"]}]},{"name":"Tucum\u00e1n National University","award":["PIP-CONICET 11220130100619CO"],"award-info":[{"award-number":["PIP-CONICET 11220130100619CO"]}]},{"name":"Tucum\u00e1n National University","award":["PICT-MINCyT 2012\u20132882"],"award-info":[{"award-number":["PICT-MINCyT 2012\u20132882"]}]},{"name":"Tucum\u00e1n National University","award":["PIUNT-UNT D542\/1"],"award-info":[{"award-number":["PIUNT-UNT D542\/1"]}]},{"name":"Tucum\u00e1n National University","award":["PICT 2018-2989"],"award-info":[{"award-number":["PICT 2018-2989"]}]},{"name":"Tucum\u00e1n National University","award":["PICT 2018-3379"],"award-info":[{"award-number":["PICT 2018-3379"]}]},{"name":"Tucum\u00e1n National University","award":["PICT 2020-2255"],"award-info":[{"award-number":["PICT 2020-2255"]}]},{"name":"Tucum\u00e1n National University","award":["PIUNT 2020"],"award-info":[{"award-number":["PIUNT 2020"]}]},{"name":"Tucum\u00e1n National University","award":["PIUNT D644\/1"],"award-info":[{"award-number":["PIUNT D644\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue \u03b1-synuclein (\u03b1-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects. The molecule was obtained by removal the dimethylamino substituent at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with \u03b1-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of \u03b1-Syn preformed fibrils (\u03b1-SynPFF) in biophysical assays and in a SH-SY5Y-\u03b1-Syn-tRFP cell model. In addition, DDMC rendered \u03b1-SynPFF less inflammogenic. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in Parkinson\u2019s disease and other synucleinopathies.<\/jats:p>","DOI":"10.3390\/cells11172759","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T23:35:57Z","timestamp":1662420957000},"page":"2759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-6009","authenticated-orcid":false,"given":"Rodrigo","family":"Tomas-Grau","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), Pasaje Dorrego 1080, San Miguel de Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Gonz\u00e1lez-Liz\u00e1rraga","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), Pasaje Dorrego 1080, San Miguel de Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Ploper","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), Pasaje Dorrego 1080, San Miguel de Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar L.","family":"Avila","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), Pasaje Dorrego 1080, San Miguel de Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-4672","authenticated-orcid":false,"given":"Sergio B.","family":"Soc\u00edas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), Pasaje Dorrego 1080, San Miguel de Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Besnault","sequence":"additional","affiliation":[{"name":"Paris Brain Institute-ICM, Inserm, CNRS, Sorbonne Universit\u00e9 APHP, H\u00f4pital de la Piti\u00e9 la Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Tourville","sequence":"additional","affiliation":[{"name":"Paris Brain Institute-ICM, Inserm, CNRS, Sorbonne Universit\u00e9 APHP, H\u00f4pital de la Piti\u00e9 la Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2522-6105","authenticated-orcid":false,"given":"Rosa M.","family":"Mella","sequence":"additional","affiliation":[{"name":"Innoprot SL, Parque Tecnol\u00f3gico de Bizkaia, Edificio 502, 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Villac\u00e9","sequence":"additional","affiliation":[{"name":"Innoprot SL, Parque Tecnol\u00f3gico de Bizkaia, Edificio 502, 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisa","family":"Salado","sequence":"additional","affiliation":[{"name":"Innoprot SL, Parque Tecnol\u00f3gico de Bizkaia, Edificio 502, 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Rose","sequence":"additional","affiliation":[{"name":"BioCIS, Universit\u00e9 Paris-Saclay, CNRS, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandine","family":"Seon-M\u00e9niel","sequence":"additional","affiliation":[{"name":"BioCIS, Universit\u00e9 Paris-Saclay, CNRS, 92290 Ch\u00e2tenay-Malabry, 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 \u201cMembranes et Cibles Th\u00e9rapeutiques\u201d, U1261 INSERM, Aix-Marseille Universit\u00e9, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-205X","authenticated-orcid":false,"given":"Laurent","family":"Ferri\u00e9","sequence":"additional","affiliation":[{"name":"BioCIS, Universit\u00e9 Paris-Saclay, CNRS, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Raisman-Vozari","sequence":"additional","affiliation":[{"name":"Paris Brain Institute-ICM, Inserm, CNRS, Sorbonne Universit\u00e9 APHP, H\u00f4pital de la Piti\u00e9 la Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5607-3119","authenticated-orcid":false,"given":"Patrick P.","family":"Michel","sequence":"additional","affiliation":[{"name":"Paris Brain Institute-ICM, Inserm, CNRS, Sorbonne Universit\u00e9 APHP, H\u00f4pital de la Piti\u00e9 la Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Figad\u00e8re","sequence":"additional","affiliation":[{"name":"BioCIS, Universit\u00e9 Paris-Saclay, CNRS, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3504-7952","authenticated-orcid":false,"given":"Rosana","family":"Cheh\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET-UNT-SIPROSA), Pasaje Dorrego 1080, San Miguel de Tucum\u00e1n 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jaad.2005.10.004","article-title":"Tetracyclines: Nonantibiotic properties and their clinical implications","volume":"54","author":"Sapadin","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s12640-015-9592-2","article-title":"Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways","volume":"29","author":"Socias","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15769","DOI":"10.1073\/pnas.95.26.15769","article-title":"Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia","volume":"95","author":"Yrjanheikki","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/jamaneurol.2016.0022","article-title":"Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study","volume":"73","author":"Egeberg","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14669","DOI":"10.1073\/pnas.251341998","article-title":"Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson\u2019s disease","volume":"98","author":"Du","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1523\/JNEUROSCI.22-05-01763.2002","article-title":"Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease","volume":"22","author":"Wu","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/WNF.0b013e3181342f32","article-title":"A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results","volume":"31","author":"Investigators","year":"2008","journal-title":"Clin. Neuropharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1007\/s12035-019-01847-8","article-title":"Neuroprotective Effects of Doxycycline in the R6\/2 Mouse Model of Huntington\u2019s Disease","volume":"57","author":"Paldino","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"635760","DOI":"10.3389\/fnagi.2021.635760","article-title":"Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity","volume":"13","author":"Medina","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41755","DOI":"10.1038\/srep41755","article-title":"Repurposing doxycycline for synucleinopathies: Remodelling of alpha-synuclein oligomers towards non-toxic parallel beta-sheet structured species","volume":"7","author":"Socias","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","first-page":"1","article-title":"CMT-3 targets different \u03b1-synuclein aggregates mitigating their toxic and inflammogenic effects","volume":"10","author":"Ploper","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/antibiotics1010001","article-title":"Classification Framework and Chemical Biology of Tetracycline-Structure-Based Drugs","volume":"1","author":"Fuoco","year":"2012","journal-title":"Antibiotics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41531-021-00195-6","article-title":"Potent inhibitors of toxic alpha-synuclein identified via cellular time-resolved FRET biosensors","volume":"7","author":"Braun","year":"2021","journal-title":"NPJ Parkinsons Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"dlac009","DOI":"10.1093\/jacamr\/dlac009","article-title":"A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora","volume":"4","author":"Truong","year":"2022","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0022-2836(02)00775-1","article-title":"Dependence of alpha-synuclein aggregate morphology on solution conditions","volume":"322","author":"Hoyer","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_16","first-page":"364","article-title":"Comite de l\u2019Antibiogramme de la Societe Francaise de Microbiologie report 2003","volume":"21","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/pro.5560020312","article-title":"Thioflavine T interaction with synthetic Alzheimer\u2019s disease beta-amyloid peptides: Detection of amyloid aggregation in solution","volume":"2","author":"LeVine","year":"1993","journal-title":"Protein Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0076-6879(99)09021-7","article-title":"Quantifying amyloid by congo red spectral shift assay","volume":"309","author":"Klunk","year":"1999","journal-title":"Methods Enzymol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41593-019-0541-x","article-title":"alpha-Synuclein strains target distinct brain regions and cell types","volume":"23","author":"Lau","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-021-04344-9","article-title":"CellProfiler 4: Improvements in speed, utility and usability","volume":"22","author":"Stirling","year":"2021","journal-title":"BMC Bioinform."},{"key":"ref_22","first-page":"1692","article-title":"FRET-Based Screening Identifies p38 MAPK and PKC Inhibition as Targets for Prevention of Seeded alpha-Synuclein Aggregation","volume":"18","author":"Svanbergsson","year":"2021","journal-title":"Neurother. J. Am. Soc. Exp. Neurother."},{"key":"ref_23","unstructured":"Angusti, A.H.S.T., Jiang, X.S., Komatsu, H., Konishi, Y., Kubo, T., Lertvorachon, J., and Roman, G. (2005). Tetracyclines and Their Use as Calpain Inhibitors. (WO2005082860A1), WIPO (PCT)."},{"key":"ref_24","unstructured":"Abato, P.A.H., Berniac, J., Bowser, T., Chen, J., Grier, M., and Honeyman, L. (2007). Tetracyclines 10-Substituees Et Leurs Procedes D\u2019utilisation. (WO2007014154A3), WIPO (PCT)."},{"key":"ref_25","unstructured":"Sucholeiki, I. (2012). Compounds and Methods for the Treatment of Pain and Other Diseases. (CN102325768A), China Patent."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pneurobio.2017.12.002","article-title":"Exploiting the therapeutic potential of ready-to-use drugs: Repurposing antibiotics against amyloid aggregation in neurodegenerative diseases","volume":"162","author":"Socias","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Edan, R.A., Luqmani, Y.A., and Masocha, W. (2013). COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057827"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3389\/fimmu.2020.00272","article-title":"Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes","volume":"11","author":"Sarkar","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.neuron.2022.01.017","article-title":"The different autophagy degradation pathways and neurodegeneration","volume":"110","author":"Fleming","year":"2022","journal-title":"Neuron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"a033993","DOI":"10.1101\/cshperspect.a033993","article-title":"The Autophagy Lysosomal Pathway and Neurodegeneration","volume":"12","author":"Finkbeiner","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eabm6393","DOI":"10.1126\/sciadv.abm6393","article-title":"Mutant glucocerebrosidase impairs alpha-synuclein degradation by blockade of chaperone-mediated autophagy","volume":"8","author":"Kuo","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8637","DOI":"10.1073\/pnas.0712179105","article-title":"The fold of alpha-synuclein fibrils","volume":"105","author":"Vilar","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.bbapap.2010.04.001","article-title":"Molecular mechanism of Thioflavin-T binding to amyloid fibrils","volume":"1804","author":"Biancalana","year":"2010","journal-title":"Biochim. Biophys Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12154-009-0027-5","article-title":"Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status","volume":"3","author":"Groenning","year":"2010","journal-title":"J. Chem. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8104","DOI":"10.1002\/anie.201916630","article-title":"On the Binding of Congo Red to Amyloid Fibrils","volume":"59","author":"Saupe","year":"2020","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8667","DOI":"10.1039\/C8CC02204F","article-title":"Secondary nucleation in amyloid formation","volume":"54","author":"Tornquist","year":"2018","journal-title":"Chem. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41586-020-2317-6","article-title":"Structures of alpha-synuclein filaments from multiple system atrophy","volume":"585","author":"Schweighauser","year":"2020","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1084\/jem.20112457","article-title":"Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice","volume":"209","author":"Luk","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/brain\/awt037","article-title":"Prion-like spreading of pathological alpha-synuclein in brain","volume":"136","author":"Nonaka","year":"2013","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20051","DOI":"10.1073\/pnas.0908005106","article-title":"Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells","volume":"106","author":"Luk","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15194","DOI":"10.1074\/jbc.M113.457408","article-title":"Lewy body-like alpha-synuclein aggregates resist degradation and impair macroautophagy","volume":"288","author":"Tanik","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1038\/nprot.2014.143","article-title":"Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy neurite-like aggregates","volume":"9","author":"Luk","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Acu\u00f1a, L., Hamadat, S., Corbal\u00e1n, N.S., Gonz\u00e1lez-Liz\u00e1rraga, F., Dos-Santos-Pereira, M., Rocca, J., D\u00edaz, J.S., Del-Bel, E., Papy-Garc\u00eda, D., and Cheh\u00edn, R.N. (2019). Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by \u03b1-Synuclein Fibrillary Aggregates. Cells, 8.","DOI":"10.3390\/cells8080776"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.chembiol.2018.08.005","article-title":"Potent alpha-Synuclein Aggregation Inhibitors, Identified by High-Throughput Screening, Mainly Target the Monomeric State","volume":"25","author":"Kurnik","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13482","DOI":"10.1074\/jbc.M117.780296","article-title":"Selective imaging of internalized proteopathic alpha-synuclein seeds in primary neurons reveals mechanistic insight into transmission of synucleinopathies","volume":"292","author":"Karpowicz","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_48","first-page":"1","article-title":"Impaired endo-lysosomal membrane integrity accelerates the seeding progression of alpha-synuclein aggregates","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"134316","DOI":"10.1016\/j.neulet.2019.134316","article-title":"alpha-Synuclein pathology in Parkinson\u2019s disease and related alpha-synucleinopathies","volume":"709","author":"Henderson","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41589-021-00768-9","article-title":"Small molecule probes for targeting autophagy","volume":"17","author":"Laraia","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Zhu, J., Wu, L., Xu, G., Dai, J., and Liu, X. (2012). Tetracycline inhibits local inflammation induced by cerebral ischemia via modulating autophagy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048672"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"112803","DOI":"10.1016\/j.biopha.2022.112803","article-title":"Minocycline treatment improves proteostasis during Drosophila aging via autophagy mediated by FOXO and Hsp70","volume":"149","author":"Lim","year":"2022","journal-title":"Biomed. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1074\/jbc.M110.178376","article-title":"Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils","volume":"286","author":"Giorgetti","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1006\/jmbi.1997.1348","article-title":"Common core structure of amyloid fibrils by synchrotron X-ray diffraction","volume":"273","author":"Sunde","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.1111\/j.1742-4658.2005.05021.x","article-title":"The Yin and Yang of protein folding","volume":"272","author":"Jahn","year":"2005","journal-title":"FEBS J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"77","DOI":"10.14802\/jmd.19046.e","article-title":"Modeling alpha-Synuclein Propagation with Preformed Fibril Injections","volume":"13","author":"Chung","year":"2020","journal-title":"J. Mov. Disord"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9808","DOI":"10.1523\/JNEUROSCI.1788-16.2017","article-title":"Prying into the Prion Hypothesis for Parkinson\u2019s Disease","volume":"37","author":"Brundin","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s12035-021-02713-2","article-title":"Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells","volume":"59","author":"Vasili","year":"2022","journal-title":"Mol. Neurobiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2759\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:18Z","timestamp":1760142198000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,4]]},"references-count":58,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cells11172759"],"URL":"https:\/\/doi.org\/10.3390\/cells11172759","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202208.0091.v1","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,4]]}}}