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The aim of the present study was to investigate potential benefits of flavonoid quercetin against copper-induced toxicity. Results obtained with MTT assay indicate that the effects of quercetin are determined by the severity of the toxic insult. In moderately injured P19 neuronal cells, concomitant treatment with 150\u2009\n                    <jats:italic>\u03bc<\/jats:italic>\n                    M quercetin improved viability by preventing ROS formation, caspase-3 activation, and chromatin condensation. Western blot analysis revealed that quercetin reduced copper-induced increase in p53 upregulated modulator of apoptosis (PUMA) expression and promoted upregulation of nucleoside diphosphate kinase NME1. Levels of p53 and Bax proteins were not affected by both copper and quercetin. UO126 and wortmannin, inhibitors of ERK1\/2 and PI3K\/Akt signalling pathways, respectively, prevented neuroprotective effects of quercetin. In severely injured neurons, 30\u2009\n                    <jats:italic>\u03bc<\/jats:italic>\n                    M quercetin exerted strong prooxidative action and exacerbated cytotoxic effects of copper, whereas 150\u2009\n                    <jats:italic>\u03bc<\/jats:italic>\n                    M quercetin failed to affect neuronal survival. These results demonstrate the dual nature of quercetin action in copper-related neurodegeneration. Hence, they are relevant in the context of considering quercetin as a possible therapeutic for neuroprotection and imply that detailed pharmacological and toxicological studies must be carried out for natural compounds capable of acting both as antioxidants and prooxidants.\n                  <\/jats:p>","DOI":"10.1155\/2020\/9834742","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T19:32:05Z","timestamp":1594495925000},"page":"1-14","source":"Crossref","is-referenced-by-count":33,"title":["PI3K\/Akt and ERK1\/2 Signalling Are Involved in Quercetin-Mediated Neuroprotection against Copper-Induced Injury"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5898-6210","authenticated-orcid":true,"given":"Klara","family":"Zub\u010di\u0107","sequence":"first","affiliation":[{"name":"Department for Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-3097","authenticated-orcid":true,"given":"Vedrana","family":"Radovanovi\u0107","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3113-420X","authenticated-orcid":true,"given":"Josipa","family":"Vlaini\u0107","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-1154","authenticated-orcid":true,"given":"Patrick R.","family":"Hof","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience, Friedman Brain Institute, and Ronald M. 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