{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:16:42Z","timestamp":1788812202423,"version":"build-2803163510"},"reference-count":89,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. U1532264 and 81741132"],"award-info":[{"award-number":["No. U1532264 and 81741132"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Oxidative stress triggers a lethal cascade, leading to Parkinson\u2019s disease by causing degeneration of dopaminergic neurons. In this study, eight antioxidants were screened for their neuroprotective effect on PC12 cells (pheochromocytoma cell line) under oxidative stress induced by salsolinol (OSibS). Hydroxytyrosol was found to be the strongest neuroprotective agent; it improved viability of PC12 cells by up to 81.69% under OSibS. Afterward, two synaptic vesicle proteins, synapsin-1 and septin-5, were screened for their neuroprotective role; the overexpression of synapsin-1 and the downregulation of septin-5 separately improved the viability of PC12 cells by up to 71.17% and 67.00%, respectively, compared to PC12 cells only treated with salsolinol (PoTwS) under OSibS. Subsequently, the PC12+syn++sep\u2212 cell line was constructed and pretreated with 100 \u00b5M hydroxytyrosol, which improved its cell viability by up to 99.03% and led to 14.71- and 6.37-fold reductions in the levels of MDA and H2O2, respectively, and 6.8-, 12.97-, 10.57-, and 7.57-fold increases in the activity of catalase, glutathione reductase, superoxide dismutase, and glutathione peroxidase, respectively, compared to PoTwS under OSibS. Finally, alcohol dehydrogenase-6 from Saccharomyces cerevisiae was expressed in PC12+syn++sep\u2212 cells to convert 3,4-dihydroxyphenylacetaldehyde (an endogenous neurotoxin) into hydroxytyrosol. The PC12+syn++sep\u2212+ADH6+ cell line also led to 22.38- and 12.33-fold decreases in the production of MDA and H2O2, respectively, and 7.15-, 13.93-, 12.08-, and 8.11-fold improvements in the activity of catalase, glutathione reductase, superoxide dismutase, and glutathione peroxidase, respectively, compared to PoTwS under OSibS. Herein, we report the endogenous production of a powerful antioxidant, hydroxytyrosol, from 3,4-dihydroxyphenylacetaldehyde, and evaluate its synergistic neuroprotective effect, along with synapsin-1 and septin-5, on PC12 cells under OSibS.<\/jats:p>","DOI":"10.3390\/molecules25071715","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T05:31:16Z","timestamp":1586496676000},"page":"1715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synergistic Neuroprotective Effect of Endogenously-Produced Hydroxytyrosol and Synaptic Vesicle Proteins on Pheochromocytoma Cell Line against Salsolinol"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-490X","authenticated-orcid":false,"given":"Robina","family":"Manzoor","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamir","family":"Rasool","sequence":"additional","affiliation":[{"name":"Institute for Synthetic Biosystem, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China"},{"name":"Institute of Biochemistry, University of Balochistan, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maqbool","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Bolan University of Medical and Health Sciences, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ullah","family":"Kaleem","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Balochistan, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5363-2421","authenticated-orcid":false,"given":"Lucienne Nneoma","family":"Duru","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Deng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.nbd.2018.04.020","article-title":"Crosstalk between presynaptic trafficking and autophagy in Parkinson\u2019s disease","volume":"122","author":"Pan","year":"2019","journal-title":"Neurobiol. 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