{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:01:23Z","timestamp":1790694083057,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,3,16]],"date-time":"2007-03-16T00:00:00Z","timestamp":1174003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2007,3,16]],"date-time":"2007-03-16T00:00:00Z","timestamp":1174003200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:p>\n                    Parkinson's disease (PD), a neurodegenerative disorder, causes severe motor impairment due to loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). MPTP, a neurotoxin that causes dopaminergic cell loss in mice, was used in an animal model to study the pathogenic mechanisms leading to neurodegeneration. We observed the activation of apoptosis signal regulating kinase (ASK1, MAPKKK) and phosphorylation of its downstream targets MKK4 and JNK, 12 h after administration of a single dose of MPTP. Further, Daxx, the death\u2010associated protein, translocated to the cytosol selectively in SNpc neurons seemingly due to MPTP mediated down\u2010regulation of DJ\u20101, the redox\u2010sensitive protein that binds Daxx in the nucleus. Coadministration of a\u2010lipoic acid (ALA), a thiol antioxidant, abolished the activation of ASK1 and phosphorylation of downstream kinases, MKK4, and JNK and prevented the down\u2010regulation of DJ\u20101 and translocation of Daxx to the cytosol seen after MPTP. ALA also attenuated dopaminergic cell loss in SNpc seen after subchronic MPTP treatment. Our studies demonstrate for the first time that MPTP triggers death signaling pathway by activating ASK1 and translocating Daxx,\n                    <jats:italic>in vivo,<\/jats:italic>\n                    in dopaminergic neurons in SNpc of mice and thiol antioxidants, such as ALA terminate this cascade and afford neuroprotection.\u2013Karunakaran S., Diwakar, L., Saeed, U., Agarwal, V., Ramakrishnan, S., Iyengar, S., Ravindranath V. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death associated protein, Daxx in substantia nigra pars compacta in a mouse model of Parkinson's disease: Protection by \u03b1\u2010lipoic acid.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    21, 2226\u20132236 (2007)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-7580com","type":"journal-article","created":{"date-parts":[[2007,3,16]],"date-time":"2007-03-16T21:40:00Z","timestamp":1174081200000},"page":"2226-2236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death\u2010associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by \u03b1\u2010lipoic acid"],"prefix":"10.1096","volume":"21","author":[{"given":"Smitha","family":"Karunakaran","sequence":"first","affiliation":[{"name":"Divisions of Molecular and Cellular Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latha","family":"Diwakar","sequence":"additional","affiliation":[{"name":"Divisions of Molecular and Cellular Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzma","family":"Saeed","sequence":"additional","affiliation":[{"name":"Divisions of Molecular and Cellular Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Divisions of Molecular and Cellular Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujanitha","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Divisions of Molecular and Cellular Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya","family":"Iyengar","sequence":"additional","affiliation":[{"name":"Divisions of Systems Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayalakshmi","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"Divisions of Molecular and Cellular Neuroscience National Brain Research Centre Manesar India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,3,16]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"13","article-title":"Brain monoamines and Parkinsonism","volume":"3","author":"Hornykiewicz O.","year":"1975","journal-title":"Natl. 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