{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:29:54Z","timestamp":1791052194881,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,7,22]],"date-time":"2005-07-22T00:00:00Z","timestamp":1121990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parkinson's disease is a debilitating neurodegenerative disease characterized by loss of midbrain dopaminergic neurons. These neurons are particularly sensitive to the neurotoxin 1\u2010methyl\u20104\u2010phenylpyridinium (MPP<jats:sup>+<\/jats:sup>), the active metabolite of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP), which causes parkinsonian syndromes in humans, monkeys and rodents. Although apoptotic cell death has been implicated in MPTP\/MPP<jats:sup>+<\/jats:sup> toxicity, several recent studies have challenged the role of caspase\u2010dependent apoptosis in dopaminergic neurons. Using the midbrain\u2010derived MN9D dopaminergic cell line, we found that MPP<jats:sup>+<\/jats:sup> treatment resulted in an active form of cell death that could not be prevented by caspase inhibitors or over\u2010expression of a dominant negative inhibitor of apoptotic protease activating factor 1\/caspase\u20109. Apoptosis inducing factor (AIF) is a mitochondrial protein that may mediate caspase\u2010independent forms of regulated cell death following its translocation to the nucleus. We found that MPP<jats:sup>+<\/jats:sup> treatment elicited nuclear translocation of AIF accompanied by large\u2010scale DNA fragmentation. To establish the role of AIF in MPP<jats:sup>+<\/jats:sup> toxicity, we constructed a DNA vector encoding a short hairpin sequence targeted against AIF. Reduction of AIF expression by RNA interference inhibited large\u2010scale DNA fragmentation and conferred significant protection against MPP<jats:sup>+<\/jats:sup> toxicity. Studies of primary mouse midbrain cultures further supported a role for AIF in caspase\u2010independent cell death in MPP<jats:sup>+<\/jats:sup>\u2010treated dopaminergic neurons.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2005.03329.x","type":"journal-article","created":{"date-parts":[[2005,8,25]],"date-time":"2005-08-25T10:35:05Z","timestamp":1124966105000},"page":"1685-1695","source":"Crossref","is-referenced-by-count":76,"title":["Apoptosis inducing factor mediates caspase\u2010independent 1\u2010methyl\u20104\u2010phenylpyridinium toxicity in dopaminergic cells"],"prefix":"10.1111","volume":"94","author":[{"given":"Charleen T.","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010hui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Signore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,8,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2002.tb00468.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301911200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-07-02637.2002"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(87)90096-4"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413224200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2002.01797.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1426-04.2004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69010232.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)90661-E"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990701)57:1<86::AID-JNR9>3.0.CO;2-E"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.2004.04132.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200202130"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.5.729"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087753"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00154-7"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(02)00428-9"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-24-09126.2000"},{"key":"e_1_2_7_20_1","first-page":"1835","article-title":"Intracellular ATP levels determine cell death fate by apoptosis or necrosis","volume":"57","author":"Eguchi Y.","year":"1997","journal-title":"Cancer Res."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5744-03.2004"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10663"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-05069.2003"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-07-02247.2001"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211821200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.09.030"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/35069004"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02864.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-04-01284.1999"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.4.1249-1259.2001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90271-2"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2000.tb00261.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.10.5789"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307130"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-24-10690.2002"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/17135"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00545-3"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(02)01371-8"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.1037"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051633998"},{"key":"e_1_2_7_41_1","doi-asserted-by":"crossref","first-page":"10 963","DOI":"10.1523\/JNEUROSCI.3461-04.2004","article-title":"Apoptosis\u2010inducing factor substitutes for caspase executioners in NMDA\u2010triggered excitotoxic neuronal death","volume":"24","author":"Wang H.","year":"2004","journal-title":"J. Neurosci."},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-20-08145.1998"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.07.021"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.08.008"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.10.937"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00975.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2003.tb00478.x"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1471-4159.2005.03329.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1471-4159.2005.03329.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T06:47:12Z","timestamp":1697006832000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1471-4159.2005.03329.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,8]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2005,9]]}},"alternative-id":["10.1111\/j.1471-4159.2005.03329.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1471-4159.2005.03329.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,8]]}}}