{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:54:18Z","timestamp":1760144058543,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"COMPETE 2020\u2014Operational Programme for Competitiveness and Internationalization and Portuguese via Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PTDC\/MED-NEU\/3644\/2020","UIDB\/04539\/2020","UIDP\/04539\/2020","LA\/P\/0058\/2020","PD\/BD\/146409\/2019","PD\/BD\/2020.06543.BD"],"award-info":[{"award-number":["PTDC\/MED-NEU\/3644\/2020","UIDB\/04539\/2020","UIDP\/04539\/2020","LA\/P\/0058\/2020","PD\/BD\/146409\/2019","PD\/BD\/2020.06543.BD"]}]},{"name":"Strategic Programs","award":["PTDC\/MED-NEU\/3644\/2020","UIDB\/04539\/2020","UIDP\/04539\/2020","LA\/P\/0058\/2020","PD\/BD\/146409\/2019","PD\/BD\/2020.06543.BD"],"award-info":[{"award-number":["PTDC\/MED-NEU\/3644\/2020","UIDB\/04539\/2020","UIDP\/04539\/2020","LA\/P\/0058\/2020","PD\/BD\/146409\/2019","PD\/BD\/2020.06543.BD"]}]},{"name":"Center for Innovative Biomedicine and Biotechnology","award":["PTDC\/MED-NEU\/3644\/2020","UIDB\/04539\/2020","UIDP\/04539\/2020","LA\/P\/0058\/2020","PD\/BD\/146409\/2019","PD\/BD\/2020.06543.BD"],"award-info":[{"award-number":["PTDC\/MED-NEU\/3644\/2020","UIDB\/04539\/2020","UIDP\/04539\/2020","LA\/P\/0058\/2020","PD\/BD\/146409\/2019","PD\/BD\/2020.06543.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder with an unknown cause. Recent research has highlighted the importance of the gut in neuronal and immune maturation through the exchange of nutrients and cellular signals. This has led to the \u201cgut-first PD\u201d hypothesis, which aims to explain many of the sporadic cases and their prodromal intestinal symptoms, such as constipation and intestinal \u03b1-synuclein (aSyn) aggregation. The link between mitochondrial dysfunction and aSyn deposition is central to PD pathophysiology, since they can also trigger pro-inflammatory signals associated with aSyn deposition, potentially contributing to the onset of PD. As mitochondria are derived from ancestral alpha-proteobacteria, other bacteria may specifically target this organelle. We sought to use Nocardia cyriacigeorgica, a bacterium previously associated with parkinsonism, and dextran sulfate sodium (DSS) as pro-inflammatory modulators to gain further insight into the onset of PD. This study indicates that aSyn aggregation plus mitochondrial dysfunction without intestinal barrier leakage are not sufficient to trigger gut-first PD.<\/jats:p>","DOI":"10.3390\/ijms25063423","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T08:17:29Z","timestamp":1710749849000},"page":"3423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nocardia\u00a0cyriacigeorgica Elicits Gut Disturbances in a Leaky Gut Model of Colitis, but Not the Harmful Cascade Leading to Gut-First Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-4167","authenticated-orcid":false,"given":"Jo\u00e3o Duarte","family":"Magalh\u00e3es","sequence":"first","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Ph.D. Programme in Biomedicine and Experimental Biology (PDBEB), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8511-5821","authenticated-orcid":false,"given":"Emanuel","family":"Candeias","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2128-296X","authenticated-orcid":false,"given":"In\u00eas","family":"Melo-Marques","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2363-8131","authenticated-orcid":false,"given":"Ant\u00f3nio E.","family":"Abreu","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Ana Raquel","family":"Pereira-Santos","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Ph.D. Programme in Biomedicine and Experimental Biology (PDBEB), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"given":"Ana Raquel","family":"Esteves","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2199-0555","authenticated-orcid":false,"given":"Sandra Morais","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-7560","authenticated-orcid":false,"given":"Nuno","family":"Empadinhas","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. 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