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Although not completely understood, several abnormal cellular events are known to be related with PD progression, such as oxidative stress, mitochondrial dysfunction and apoptosis. Accordingly, the aim of this study was to evaluate the neuroprotective effects of Codium tomentosum enriched fractions in a neurotoxicity model mediated by 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, and the disclosure of their mechanisms of action. Additionally, a preliminary chemical screening of the most promising bioactive fractions of C. tomentosum was carried out by GC-MS analysis. Among the tested fractions, four samples exhibited the capacity to revert the neurotoxicity induced by 6-OHDA to values higher or similar to the vitamin E (90.11 \u00b1 3.74% of viable cells). The neuroprotective effects were mediated by the mitigation of reactive oxygen species (ROS) generation, mitochondrial dysfunctions and DNA damage, together with the reduction of Caspase-3 activity. Compounds belonging to different chemical classes, such as terpenes, alcohols, carboxylic acids, aldehydes, esters, ketones, saturated and unsaturated hydrocarbons were tentatively identified by GC-MS. The results show that C. tomentosum is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics.<\/jats:p>","DOI":"10.3390\/molecules25225478","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T11:50:34Z","timestamp":1606132234000},"page":"5478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Natural Approaches for Neurological Disorders\u2014The Neuroprotective Potential of Codium tomentosum"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-1699","authenticated-orcid":false,"given":"Joana","family":"Silva","sequence":"first","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal"},{"name":"Department of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Martins","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-2127","authenticated-orcid":false,"given":"Celso","family":"Alves","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-3111","authenticated-orcid":false,"given":"Susete","family":"Pinteus","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1613-7023","authenticated-orcid":false,"given":"Helena","family":"Gaspar","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal"},{"name":"BioISI\u2014Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1572-9016","authenticated-orcid":false,"given":"Amparo","family":"Alfonso","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, 2520-630 Peniche, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3390\/md9050803","article-title":"Neuroprotective effects of marine algae","volume":"9","author":"Pangestuti","year":"2011","journal-title":"Mar. 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