{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:53:55Z","timestamp":1773341635083,"version":"3.50.1"},"reference-count":88,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UID\/04033\/2025"],"award-info":[{"award-number":["UID\/04033\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["LA\/P\/0126\/2020"],"award-info":[{"award-number":["LA\/P\/0126\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT\/MCTES"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by mitochondrial dysfunction, oxidative stress, and apoptosis. Natural products rich in polyphenols have been investigated for their potential to modulate pathways associated with PD-related pathology. The present study evaluated the effects of an acetonic almond skin extract, an agri-food by-product, in a zebrafish (Danio rerio) larval model of PD induced by 6-hydroxydopamine (6-OHDA). Embryos were exposed to 250 \u00b5M 6-OHDA alone or in combination with the extract (5 and 25 \u00b5g\/mL) from 48 to 120 h post-fertilization (hpf). Developmental parameters, locomotor behaviour, oxidative stress biomarkers, apoptosis, mitochondrial membrane potential, and tyrosine hydroxylase (TH) immunoreactivity were assessed at 120 hpf. Exposure to 6-OHDA reduced TH immunofluorescence and impaired locomotor performance, accompanied by increased apoptotic signal and mild alterations in mitochondrial membrane potential. Co-exposure to the almond skin extract attenuated the reduction in TH immunoreactivity and partially modulated behavioural outcomes in a concentration-dependent manner. The extract alone increased glutathione S-transferase (GST) activity and reduced reactive oxygen species (ROS) levels, suggesting modulation of redox-related pathways. Notably, the highest concentration restored the TH signal but did not fully normalize the behavioural endpoints, indicating potential concentration-dependent complexity. Although sustained oxidative stress was not detected at the assessed time point, the observed mitochondrial and apoptotic alterations suggest involvement of multiple cellular processes. However, detailed mechanistic pathways were not directly investigated. Overall, these findings indicate that the almond skin extract modulates dopaminergic and behavioural alterations in a PD-induced zebrafish model, supporting its potential as a source of bioactive compounds, warranting further mechanistic and translational investigation.<\/jats:p>","DOI":"10.3390\/ijms27062590","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:23:03Z","timestamp":1773307383000},"page":"2590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amelioration of 6-OHDA-Induced Parkinson\u2019s Symptoms in Zebrafish Larvae by an Almond Skin Acetonic Extract"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6885-7444","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Carneiro","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences (ECVA), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"given":"Patricia","family":"Pais","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences (ECVA), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0866-953X","authenticated-orcid":false,"given":"Ivo Vaz","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-5965","authenticated-orcid":false,"given":"Sandra M.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3880-3442","authenticated-orcid":false,"given":"Carlos","family":"Ven\u00e2ncio","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-6666","authenticated-orcid":false,"given":"Lu\u00eds","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1016\/j.parkreldis.2017.07.033","article-title":"Neuropathology of Parkinson Disease","volume":"46","author":"Dickson","year":"2018","journal-title":"Park. 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