{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:25:53Z","timestamp":1791980753103,"version":"4.4.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"8","license":[{"start":{"date-parts":[[2009,8,24]],"date-time":"2009-08-24T00:00:00Z","timestamp":1251072000000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,2,24]]},"abstract":"<jats:p>\n                    Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. It is known that under conditions of oxidative stress, the transcription factor NF-E2-related factor (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes. To investigate the role of Nrf2 in the process of MPTP-induced toxicity, mice expressing the human placental alkaline phosphatase (hPAP) gene driven by a promoter containing a core ARE sequence (ARE-hPAP) were used. ARE-hPAP mice were injected (30 mg\/kg) once per day for 5 days and killed 7 days after the last MPTP injection. In response to this design, ARE-dependent gene expression was decreased in striatum whereas it was increased in substantia nigra. The same MPTP protocol was applied in Nrf2\n                    <jats:sup>+\/+<\/jats:sup>\n                    and Nrf2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice; Nrf2 deficiency increases MPTP sensitivity. Furthermore, we evaluated the potential for astrocytic Nrf2 overexpression to protect from MPTP toxicity. Transgenic mice with Nrf2 under control of the astrocyte-specific promoter for the glial fribillary acidic protein (GFAP-Nrf2) on both a Nrf2\n                    <jats:sup>+\/+<\/jats:sup>\n                    and Nrf2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    background were administered MPTP. In the latter case, only the astrocytes expressed Nrf2. Independent of background, MPTP-mediated toxicity was abolished in GFAP-Nrf2 mice. These striking results indicate that Nrf2 expression restricted to astrocytes is sufficient to protect against MPTP and astrocytic modulation of the Nrf2-ARE pathway is a promising target for therapeutics aimed at reducing or preventing neuronal death in PD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0813361106","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T00:06:11Z","timestamp":1233965171000},"page":"2933-2938","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":522,"title":["Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte"],"prefix":"10.1073","volume":"106","author":[{"given":"Pei-Chun","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmacy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo R.","family":"Vargas","sequence":"additional","affiliation":[{"name":"School of Pharmacy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar K.","family":"Pani","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Smeyne","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delinda A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"School of Pharmacy,"},{"name":"Molecular and Environmental Toxicology Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuet Wai","family":"Kan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute and Departments of Laboratory Medicine and Medicine, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"School of Pharmacy,"},{"name":"Molecular and Environmental Toxicology Center,"},{"name":"Waisman Center, and"},{"name":"Center of Neuroscience, University of Wisconsin, Madison, WI 53705;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,2,24]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"342","article-title":"Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine","volume":"13","author":"Chiba K","year":"1985","unstructured":"K Chiba, LA Peterson, KP Castagnoli, AJ Trevor, N Castagnoli, Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 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