{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T18:00:47Z","timestamp":1775325647753,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-FAR\/29391\/2017, POCI-01-0145-FEDER-029391, PTDC\/BTM-SAL\/29297\/2017, PO-CI-01-0145-FEDER-029297, PTDC\/BTM-ORG\/0055\/2021, DL57\/2016\/CP1448\/CT0016 [TCO], UIDP\/04539\/2020 (CNC), UIDB\/04539\/2020 (CNC), and UID\/CEC\/00326\/2020 (CISUC)"],"award-info":[{"award-number":["PTDC\/MED-FAR\/29391\/2017, POCI-01-0145-FEDER-029391, PTDC\/BTM-SAL\/29297\/2017, PO-CI-01-0145-FEDER-029297, PTDC\/BTM-ORG\/0055\/2021, DL57\/2016\/CP1448\/CT0016 [TCO], UIDP\/04539\/2020 (CNC), UIDB\/04539\/2020 (CNC), and UID\/CEC\/00326\/2020 (CISUC)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>With the increase in life expectancy and consequent aging of the world\u2019s population, the prevalence of many neurodegenerative diseases is increasing, without concomitant improvement in diagnostics and therapeutics. These diseases share neuropathological hallmarks, including mitochondrial dysfunction. In fact, as mitochondrial alterations appear prior to neuronal cell death at an early phase of a disease\u2019s onset, the study and modulation of mitochondrial alterations have emerged as promising strategies to predict and prevent neurotoxicity and neuronal cell death before the onset of cell viability alterations. In this work, differentiated SH-SY5Y cells were treated with the mitochondrial-targeted neurotoxicants 6-hydroxydopamine and rotenone. These compounds were used at different concentrations and for different time points to understand the similarities and differences in their mechanisms of action. To accomplish this, data on mitochondrial parameters were acquired and analyzed using unsupervised (hierarchical clustering) and supervised (decision tree) machine learning methods. Both biochemical and computational analyses resulted in an evident distinction between the neurotoxic effects of 6-hydroxydopamine and rotenone, specifically for the highest concentrations of both compounds.<\/jats:p>","DOI":"10.3390\/ijms23063009","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"3009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2718-9950","authenticated-orcid":false,"given":"Rui F.","family":"Sim\u00f5es","sequence":"first","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Programme in Experimental Biology and Biomedicine (PDBEB), Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5201-9948","authenticated-orcid":false,"given":"Paulo J.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7382-0339","authenticated-orcid":false,"given":"Teresa","family":"Cunha-Oliveira","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-6548","authenticated-orcid":false,"given":"Francisco B.","family":"Pereira","sequence":"additional","affiliation":[{"name":"CISUC, Centre for Informatics & Systems, University of Coimbra, 3030-299 Coimbra, Portugal"},{"name":"Polytechnic Institute of Coimbra, Coimbra Institute of Engineering, 3030-190 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nj7526-299a","article-title":"Neurodegenerative disease: Brain windfall","volume":"515","author":"Gammon","year":"2014","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a028035","DOI":"10.1101\/cshperspect.a028035","article-title":"Pathology of Neurodegenerative Diseases","volume":"9","author":"Dugger","year":"2017","journal-title":"Cold Spring Harb. 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