{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:50:15Z","timestamp":1791039015152,"version":"4.1.0"},"reference-count":62,"publisher":"Society for Neuroscience","issue":"16","license":[{"start":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T00:00:00Z","timestamp":1192665600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,4,18]]},"abstract":"<jats:p>Parkinson's disease (PD) is an age-related neurodegenerative disease in which the role of reactive oxygen species (ROS) is strongly implicated. The presence of oxidative stress has been detected in human and experimental PD using both direct and indirect indices. Scavenging ROS is, therefore, an important therapeutic avenue for the treatment of PD. Manganic porphyrins are catalytic antioxidants that scavenge a wide range of ROS. In this study, we tested the therapeutic effects of a compound [5,15-bis(methoxycarbonyl)-10,20-bis-trifluoromethyl-porphyrinato manganese (III) chloride (AEOL11207)] belonging to a new generation of lipophilic manganic porphyrins for neuroprotection and oral bioavailability in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. Groups of adult C57BL\/6 mice were administered MPTP with varying subcutaneous or oral dosing regimens of AEOL11207. Neurotoxicity was assessed by measurement of striatal dopamine levels and quantification of tyrosine hydroxylase-positive neurons in the substantial nigra<jats:italic>pars compacta<\/jats:italic>one week after the first dose of MPTP. Glutathione depletion, lipid peroxidation, and 3-nitrotyrosine (3-NT) formation were measured as indicators of oxidative stress in the ventral midbrain<jats:italic>in vivo<\/jats:italic>. AEOL11207 administered either by subcutaneous or oral routes protected against MPTP-induced dopamine depletion in the striatum as well as dopaminergic neuronal loss, glutathione depletion, lipid peroxidation, and 3-NT formation in the ventral midbrain. Neuroprotection correlated with brain metalloporphyrin concentrations. This is the first demonstration of neuroprotection by an orally active catalytic antioxidant in the MPTP mouse model and suggests its potential clinical utility for the treatment of chronic neurodegenerative diseases such as PD.<\/jats:p>","DOI":"10.1523\/jneurosci.0019-07.2007","type":"journal-article","created":{"date-parts":[[2007,4,18]],"date-time":"2007-04-18T16:48:03Z","timestamp":1176914883000},"page":"4326-4333","source":"Crossref","is-referenced-by-count":80,"title":["An Orally Active Catalytic Metalloporphyrin Protects against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity<i>In Vivo<\/i>"],"prefix":"10.1523","volume":"27","author":[{"given":"Li-Ping","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Fulton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,4,18]]},"reference":[{"key":"2023041303245862000_27.16.4326.1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1046\/j.1471-4159.1997.69031196.x","article-title":"Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra","volume":"69","author":"Alam","year":"1997","journal-title":"J Neurochem"},{"key":"2023041303245862000_27.16.4326.2","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1046\/j.1471-4159.1997.69031326.x","article-title":"A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease","volume":"69","author":"Alam","year":"1997","journal-title":"J Neurochem"},{"key":"2023041303245862000_27.16.4326.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7659"},{"key":"2023041303245862000_27.16.4326.4","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(84)90682-8"},{"key":"2023041303245862000_27.16.4326.5","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0005-2728(98)00114-5","article-title":"Mitochondrial dysfunction in neurodegenerative diseases","volume":"1366","author":"Beal","year":"1998","journal-title":"Biochim Biophys Acta"},{"key":"2023041303245862000_27.16.4326.6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/35072550","article-title":"Experimental models of Parkinson's disease","volume":"2","author":"Beal","year":"2001","journal-title":"Nat Rev Neurosci"},{"key":"2023041303245862000_27.16.4326.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00780-3"},{"key":"2023041303245862000_27.16.4326.8","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20624"},{"key":"2023041303245862000_27.16.4326.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb03143.x"},{"key":"2023041303245862000_27.16.4326.10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0005-2760(80)90209-X","article-title":"Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids","volume":"620","author":"Benedetti","year":"1980","journal-title":"Biochim Biophys Acta"},{"key":"2023041303245862000_27.16.4326.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0970-05.2005"},{"key":"2023041303245862000_27.16.4326.12","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20552"},{"key":"2023041303245862000_27.16.4326.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"2023041303245862000_27.16.4326.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91361-4"},{"key":"2023041303245862000_27.16.4326.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1989.tb09133.x"},{"key":"2023041303245862000_27.16.4326.16","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870090115"},{"key":"2023041303245862000_27.16.4326.17","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350107"},{"key":"2023041303245862000_27.16.4326.18","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(91)90192-6"},{"key":"2023041303245862000_27.16.4326.19","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(86)90205-4"},{"key":"2023041303245862000_27.16.4326.20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1046\/j.1471-4159.2003.01709.x","article-title":"Isofurans, but not F2-isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body disease","volume":"85","author":"Fessel","year":"2003","journal-title":"J Neurochem"},{"key":"2023041303245862000_27.16.4326.21","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1523\/JNEUROSCI.23-04-01228.2003","article-title":"Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease","volume":"23","author":"Gao","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303245862000_27.16.4326.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(02)00153-0"},{"key":"2023041303245862000_27.16.4326.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5493.985"},{"key":"2023041303245862000_27.16.4326.24","first-page":"691","article-title":"Correlation between the neostriatal content of the 1-methyl-4-phenylpyridinium species and dopaminergic neurotoxicity following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration to several strains of mice","volume":"257","author":"Giovanni","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303245862000_27.16.4326.25","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199804000-00006"},{"key":"2023041303245862000_27.16.4326.26","doi-asserted-by":"crossref","first-page":"8126","DOI":"10.1523\/JNEUROSCI.18-20-08126.1998","article-title":"Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation","volume":"18","author":"Hensley","year":"1998","journal-title":"J Neurosci"},{"key":"2023041303245862000_27.16.4326.27","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(92)90431-U"},{"key":"2023041303245862000_27.16.4326.28","doi-asserted-by":"publisher","DOI":"10.1007\/BF02252926"},{"key":"2023041303245862000_27.16.4326.29","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320714"},{"key":"2023041303245862000_27.16.4326.30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000120200"},{"key":"2023041303245862000_27.16.4326.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(01)00531-X"},{"key":"2023041303245862000_27.16.4326.32","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0191"},{"key":"2023041303245862000_27.16.4326.33","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1997.2032"},{"key":"2023041303245862000_27.16.4326.34","doi-asserted-by":"publisher","DOI":"10.1007\/BF01291883"},{"key":"2023041303245862000_27.16.4326.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02567.x"},{"key":"2023041303245862000_27.16.4326.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.08.026"},{"key":"2023041303245862000_27.16.4326.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00397-3"},{"key":"2023041303245862000_27.16.4326.38","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1523\/JNEUROSCI.21-13-04582.2001","article-title":"Neuroprotection from delayed postischemic administration of a metalloporphyrin catalytic antioxidant","volume":"21","author":"Mackensen","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303245862000_27.16.4326.39","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/94.9.485"},{"key":"2023041303245862000_27.16.4326.40","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.52.070183.003431"},{"key":"2023041303245862000_27.16.4326.41","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J Biol Chem"},{"key":"2023041303245862000_27.16.4326.42","doi-asserted-by":"publisher","DOI":"10.1016\/0009-3084(95)02506-5"},{"key":"2023041303245862000_27.16.4326.43","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01628.x"},{"key":"2023041303245862000_27.16.4326.44","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(99)01336-X"},{"key":"2023041303245862000_27.16.4326.45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.49.34621"},{"key":"2023041303245862000_27.16.4326.46","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(82)90390-1"},{"key":"2023041303245862000_27.16.4326.47","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1523\/JNEUROSCI.12-05-01658.1992","article-title":"Transgenic mice with increased Cu\/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity","volume":"12","author":"Przedborski","year":"1992","journal-title":"J Neurosci"},{"key":"2023041303245862000_27.16.4326.48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00183.x"},{"key":"2023041303245862000_27.16.4326.49","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00174.x"},{"key":"2023041303245862000_27.16.4326.50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0925-4439(95)00008-R","article-title":"Influence of metabolic inhibitors on mitochondrial permeability transition and glutathione status","volume":"1271","author":"Reed","year":"1995","journal-title":"Biochim Biophys Acta"},{"key":"2023041303245862000_27.16.4326.51","doi-asserted-by":"publisher","DOI":"10.2174\/0929867013372922"},{"key":"2023041303245862000_27.16.4326.52","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0140-6736(89)92366-0","article-title":"Mitochondrial complex I deficiency in Parkinson's disease.[comment]","volume":"1","author":"Schapira","year":"1989","journal-title":"Lancet"},{"key":"2023041303245862000_27.16.4326.53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb02325.x"},{"key":"2023041303245862000_27.16.4326.54","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1042\/bst0210367","article-title":"Free radicals and mitochondrial dysfunction in Parkinson's disease","volume":"21","author":"Schapira","year":"1993","journal-title":"Biochem Soc Trans"},{"key":"2023041303245862000_27.16.4326.55","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1046\/j.1471-4159.1995.64020936.x","article-title":"Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice","volume":"64","author":"Schulz","year":"1995","journal-title":"J Neurochem"},{"key":"2023041303245862000_27.16.4326.56","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00021-5"},{"key":"2023041303245862000_27.16.4326.57","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360305"},{"key":"2023041303245862000_27.16.4326.58","doi-asserted-by":"publisher","DOI":"10.1007\/BF01244786"},{"key":"2023041303245862000_27.16.4326.59","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(03)00272-4"},{"key":"2023041303245862000_27.16.4326.60","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01362-9"},{"key":"2023041303245862000_27.16.4326.61","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0937239100"},{"key":"2023041303245862000_27.16.4326.62","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.7.2696"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0019-07.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T17:57:58Z","timestamp":1681408678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0019-07.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,18]]},"references-count":62,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2007,4,18]]},"published-print":{"date-parts":[[2007,4,18]]}},"alternative-id":["10.1523\/JNEUROSCI.0019-07.2007"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0019-07.2007","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,18]]}}}