{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:35:06Z","timestamp":1791128106800,"version":"4.1.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p>\n                    Although the etiology of Parkinson's disease (PD) remains unclear, ample empirical evidence suggests that oxidative stress is a major player in the development of PD and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. Nuclear factor E2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that upregulates a battery of antioxidant response element (ARE)-driven antioxidative and cytoprotective genes that defend against oxidative stress.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    We evaluated whether the strategy of activation of Nrf2 and its downstream network of cytoprotective genes with small molecule synthetic triterpenoids (TP) attenuate MPTP-induced PD in mice.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    We show that synthetic TP are thus far the most potent and direct activators of the Nrf2 pathway using a novel Neh2-luciferase reporter. They upregulate several cytoprotective genes, including those involved in glutathione biosynthesis\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . Oral administration of TP that were structurally modified to penetrate the brain-induced messenger RNA and protein levels for a battery of Nrf2-dependent cytoprotective genes reduced MPTP-induced oxidative stress and inflammation, and ameliorated dopaminergic neurotoxicity in mice. The neuroprotective effect of these TP against MPTP neurotoxicity was dependent on Nrf2, since treatment with TP in Nrf2 knockout mice failed to block against MPTP neurotoxicity and induce Nrf2-dependent cytoprotective genes.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    Extremely potent synthetic TP that are direct activators of the Nrf2 pathway block dopaminergic neurodegeneration in the MPTP mouse model of PD.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    Our results indicate that activation of Nrf2\/antioxidant response element (ARE) signaling by synthetic TP is directly associated with their neuroprotective effects against MPTP neurotoxicity and suggest that targeting the Nrf2\/ARE pathway is a promising approach for therapeutic intervention in PD.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    18, 139\u2013157.\n                  <\/jats:p>","DOI":"10.1089\/ars.2011.4491","type":"journal-article","created":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T11:32:08Z","timestamp":1341142328000},"page":"139-157","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":155,"title":["Targeting Nrf2-Mediated Gene Transcription by Extremely Potent Synthetic Triterpenoids Attenuate Dopaminergic Neurotoxicity in the MPTP Mouse Model of Parkinson's Disease"],"prefix":"10.1177","volume":"18","author":[{"given":"Navneet Ammal","family":"Kaidery","sequence":"first","affiliation":[{"name":"Georgia Health Sciences University","place":["Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya A.","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Burke Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry M.","family":"Hushpulian","sequence":"additional","affiliation":[{"name":"Moscow State University","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen T.","family":"Liby","sequence":"additional","affiliation":[{"name":"Dartmouth Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Dartmouth Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Tohoku University","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Kensler","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv R.","family":"Ratan","sequence":"additional","affiliation":[{"name":"Burke Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Sporn","sequence":"additional","affiliation":[{"name":"Dartmouth Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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