{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:55:24Z","timestamp":1791320124138,"version":"4.3.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T00:00:00Z","timestamp":1446163200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Differ"],"published-print":{"date-parts":[[2016,3]]},"DOI":"10.1038\/cdd.2015.135","type":"journal-article","created":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T13:01:20Z","timestamp":1446210080000},"page":"542-552","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["c-Abl\u2013p38\u03b1 signaling plays an important role in MPTP-induced neuronal death"],"prefix":"10.1038","volume":"23","author":[{"given":"R","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,30]]},"reference":[{"key":"BFcdd2015135_CR1","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1172\/JCI29178","volume":"116","author":"JM Savitt","year":"2006","unstructured":"Savitt JM, Dawson VL, Dawson TM . Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 2006; 116: 1744\u20131754.","journal-title":"J Clin Invest"},{"key":"BFcdd2015135_CR2","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1017\/S1462399409001148","volume":"11","author":"T Gasser","year":"2009","unstructured":"Gasser T . Molecular pathogenesis of Parkinson disease: insights from genetic studies. Exp Rev Mol Med 2009; 11: e22.","journal-title":"Exp Rev Mol Med"},{"key":"BFcdd2015135_CR3","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","volume":"39","author":"W Dauer","year":"2003","unstructured":"Dauer W, Przedborski S . Parkinson's disease: mechanisms and models. Neuron 2003; 39: 889\u2013909.","journal-title":"Neuron"},{"key":"BFcdd2015135_CR4","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1126\/science.6823561","volume":"219","author":"JW Langston","year":"1983","unstructured":"Langston JW, Ballard P, Tetrud JW, Irwin I . Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979\u2013980.","journal-title":"Science"},{"key":"BFcdd2015135_CR5","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1042\/BC20080020","volume":"100","author":"A Sirvent","year":"2008","unstructured":"Sirvent A, Benistant C, Roche S . Cytoplasmic signalling by the c-Abl tyrosine kinase in normal and cancer cells. Biol Cell 2008; 100: 617\u2013631.","journal-title":"Biol Cell"},{"key":"BFcdd2015135_CR6","doi-asserted-by":"publisher","first-page":"9611","DOI":"10.1523\/JNEUROSCI.0035-11.2011","volume":"31","author":"L Xiao","year":"2011","unstructured":"Xiao L, Chen D, Hu P, Wu J, Liu W, Zhao Y et al. The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell death. J Neurosci 2011; 31: 9611\u20139619.","journal-title":"J Neurosci"},{"key":"BFcdd2015135_CR7","doi-asserted-by":"publisher","first-page":"e36562","DOI":"10.1371\/journal.pone.0036562","volume":"7","author":"W Liu","year":"2012","unstructured":"Liu W, Wu J, Xiao L, Bai Y, Qu A, Zheng Z et al. Regulation of neuronal cell death by c-Abl-Hippo\/MST2 signaling pathway. PLoS One 2012; 7: e36562.","journal-title":"PLoS One"},{"key":"BFcdd2015135_CR8","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1016\/j.neurobiolaging.2009.07.007","volume":"32","author":"GI Cancino","year":"2011","unstructured":"Cancino GI, Perez de Arce K, Castro PU, Toledo EM, von Bernhardi R, Alvarez AR . c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice. Neurobiol Aging 2011; 32: 1249\u20131261.","journal-title":"Neurobiol Aging"},{"key":"BFcdd2015135_CR9","doi-asserted-by":"publisher","first-page":"16691","DOI":"10.1073\/pnas.1006083107","volume":"107","author":"HS Ko","year":"2010","unstructured":"Ko HS, Lee Y, Shin JH, Karuppagounder SS, Gadad BS, Koleske AJ et al. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function. Proc Natl Acad Sci USA 2010; 107: 16691\u201316696.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcdd2015135_CR10","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1523\/JNEUROSCI.1833-10.2011","volume":"31","author":"SZ Imam","year":"2011","unstructured":"Imam SZ, Zhou Q, Yamamoto A, Valente AJ, Ali SF, Bains M et al. Novel regulation of parkin function through c-Abl-mediated tyrosine phosphorylation: implications for Parkinson's disease. J Neurosci 2011; 31: 157\u2013163.","journal-title":"J Neurosci"},{"key":"BFcdd2015135_CR11","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1093\/hmg\/ddt674","volume":"23","author":"AL Mahul-Mellier","year":"2014","unstructured":"Mahul-Mellier AL, Fauvet B, Gysbers A, Dikiy I, Oueslati A, Georgeon S et al. c-Abl phosphorylates alpha-synuclein and regulates its degradation: implication for alpha-synuclein clearance and contribution to the pathogenesis of Parkinson's disease. Hum Mol Genet 2014; 23: 2858\u20132879.","journal-title":"Hum Mol Genet"},{"key":"BFcdd2015135_CR12","doi-asserted-by":"publisher","first-page":"3315","DOI":"10.1093\/hmg\/ddt192","volume":"22","author":"ML Hebron","year":"2013","unstructured":"Hebron ML, Lonskaya I, Moussa CE . Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of alpha-synuclein in Parkinson's disease models. Hum Mol Genet 2013; 22: 3315\u20133328.","journal-title":"Hum Mol Genet"},{"key":"BFcdd2015135_CR13","doi-asserted-by":"publisher","first-page":"e65129","DOI":"10.1371\/journal.pone.0065129","volume":"8","author":"SZ Imam","year":"2013","unstructured":"Imam SZ, Trickler W, Kimura S, Binienda ZK, Paule MG, Slikker W Jr et al. Neuroprotective efficacy of a new brain-penetrating C-Abl inhibitor in a murine Parkinson's disease model. PLoS One 2013; 8: e65129.","journal-title":"PLoS One"},{"key":"BFcdd2015135_CR14","doi-asserted-by":"publisher","first-page":"4874","DOI":"10.1038\/srep04874","volume":"4","author":"SS Karuppagounder","year":"2014","unstructured":"Karuppagounder SS, Brahmachari S, Lee Y, Dawson VL, Dawson TM, Ko HS . The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson's disease. Sci Rep 2014; 4: 4874.","journal-title":"Sci Rep"},{"key":"BFcdd2015135_CR15","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1124\/jpet.102.045260","volume":"304","author":"H Dai","year":"2003","unstructured":"Dai H, Marbach P, Lemaire M, Hayes M, Elmquist WF . Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated efflux. J Pharmacol Exp Ther 2003; 304: 1085\u20131092.","journal-title":"J Pharmacol Exp Ther"},{"key":"BFcdd2015135_CR16","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1093\/hmg\/ddt674","volume":"23","author":"AL Mahul-Mellier","year":"2014","unstructured":"Mahul-Mellier AL, Fauvet B, Gysbers A, Dikiy I, Oueslati A, Georgeon S et al. c-Abl phosphorylates alpha-syn and regulates its degradation, implication for alpha-syn clearance and contribution to the pathogenesis of Parkinson's Disease. Hum Mol Genet 2014; 23: 2858\u20132879.","journal-title":"Hum Mol Genet"},{"key":"BFcdd2015135_CR17","doi-asserted-by":"publisher","first-page":"12961","DOI":"10.1074\/jbc.M300058200","volume":"278","author":"C Cao","year":"2003","unstructured":"Cao C, Leng Y, Li C, Kufe D . Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the oxidative stress response. J Biol Chem 2003; 278: 12961\u201312967.","journal-title":"J Biol Chem"},{"key":"BFcdd2015135_CR18","first-page":"1153","volume":"23","author":"A Gotoh","year":"1995","unstructured":"Gotoh A, Miyazawa K, Ohyashiki K, Tauchi T, Boswell HS, Broxmeyer HE et al. Tyrosine phosphorylation and activation of focal adhesion kinase (p125FAK) by BCR-ABL oncoprotein. Exp Hematol 1995; 23: 1153\u20131159.","journal-title":"Exp Hematol"},{"key":"BFcdd2015135_CR19","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/S0898-6568(02)00090-6","volume":"15","author":"AR Sanguinetti","year":"2003","unstructured":"Sanguinetti AR, Mastick CC . c-Abl is required for oxidative stress-induced phosphorylation of caveolin-1 on tyrosine 14. Cell Signal 2003; 15: 289\u2013298.","journal-title":"Cell Signal"},{"key":"BFcdd2015135_CR20","doi-asserted-by":"publisher","first-page":"8834","DOI":"10.1128\/MCB.25.20.8834-8843.2005","volume":"25","author":"EA Burton","year":"2005","unstructured":"Burton EA, Oliver TN, Pendergast AM . Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway. Mol Cell Biol 2005; 25: 8834\u20138843.","journal-title":"Mol Cell Biol"},{"key":"BFcdd2015135_CR21","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.jmb.2011.06.013","volume":"411","author":"U Rothweiler","year":"2011","unstructured":"Rothweiler U, Aberg E, Johnson KA, Hansen TE, Jorgensen JB, Engh RA . p38alpha MAP kinase dimers with swapped activation segments and a novel catalytic loop conformation. J Mol Biol 2011; 411: 474\u2013485.","journal-title":"J Mol Biol"},{"key":"BFcdd2015135_CR22","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1002\/gene.1078","volume":"31","author":"E Casanova","year":"2001","unstructured":"Casanova E, Fehsenfeld S, Mantamadiotis T, Lemberger T, Greiner E, Stewart AF et al. A CamKIIalpha iCre BAC allows brain-specific gene inactivation. Genesis 2001; 31: 37\u201342.","journal-title":"Genesis"},{"key":"BFcdd2015135_CR23","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S0162-3109(98)00022-8","volume":"39","author":"M Kohutnicka","year":"1998","unstructured":"Kohutnicka M, Lewandowska E, Kurkowska-Jastrzebska I, Czlonkowski A, Czlonkowska A . Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology 1998; 39: 167\u2013180.","journal-title":"Immunopharmacology"},{"key":"BFcdd2015135_CR24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrm1280","volume":"5","author":"O Hantschel","year":"2004","unstructured":"Hantschel O, Superti-Furga G . Regulation of the c-Abl and Bcr-Abl tyrosine kinases. Nat Rev Mol Cell Biol 2004; 5: 33\u201344.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcdd2015135_CR25","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/S0301-472X(00)00142-9","volume":"28","author":"SB Marley","year":"2000","unstructured":"Marley SB, Deininger MW, Davidson RJ, Goldman JM, Gordon MY . The tyrosine kinase inhibitor STI571, like interferon-alpha, preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors from patients with chronic myeloid leukemia. Exp Hematol 2000; 28: 551\u2013557.","journal-title":"Exp Hematol"},{"key":"BFcdd2015135_CR26","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s12031-011-9588-1","volume":"45","author":"SD Schlatterer","year":"2011","unstructured":"Schlatterer SD, Acker CM, Davies P . c-Abl in neurodegenerative disease. J Mol Neurosci 2011; 45: 445\u2013452.","journal-title":"J Mol Neurosci"},{"key":"BFcdd2015135_CR27","doi-asserted-by":"publisher","first-page":"4290","DOI":"10.1038\/sj.onc.1203784","volume":"19","author":"AM Johnston","year":"2000","unstructured":"Johnston AM, Naselli G, Gonez LJ, Martin RM, Harrison LC, DeAizpurua HJ . SPAK, a STE20\/SPS1-related kinase that activates the p38 pathway. Oncogene 2000; 19: 4290\u20134297.","journal-title":"Oncogene"},{"key":"BFcdd2015135_CR28","doi-asserted-by":"publisher","first-page":"6259","DOI":"10.1074\/jbc.M109.038570","volume":"285","author":"W Bi","year":"2010","unstructured":"Bi W, Xiao L, Jia Y, Wu J, Xie Q, Ren J et al. c-Jun N-terminal kinase enhances MST1-mediated pro-apoptotic signaling through phosphorylation at serine 82. J Biol Chem 2010; 285: 6259\u20136264.","journal-title":"J Biol Chem"},{"key":"BFcdd2015135_CR29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/sj.cr.7290257","volume":"15","author":"T Zarubin","year":"2005","unstructured":"Zarubin T, Han J . Activation and signaling of the p38 MAP kinase pathway. Cell Res 2005; 15: 11\u201318.","journal-title":"Cell Res"},{"key":"BFcdd2015135_CR30","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1074\/jbc.273.3.1741","volume":"273","author":"H Enslen","year":"1998","unstructured":"Enslen H, Raingeaud J, Davis RJ . Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. J Biol Chem 1998; 273: 1741\u20131748.","journal-title":"J Biol Chem"},{"key":"BFcdd2015135_CR31","doi-asserted-by":"publisher","first-page":"15469","DOI":"10.1074\/jbc.M901004200","volume":"284","author":"PR Mittelstadt","year":"2009","unstructured":"Mittelstadt PR, Yamaguchi H, Appella E, Ashwell JD . T cell receptor-mediated activation of p38{alpha} by mono-phosphorylation of the activation loop results in altered substrate specificity. J Biol Chem 2009; 284: 15469\u201315474.","journal-title":"J Biol Chem"},{"key":"BFcdd2015135_CR32","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nprot.2006.342","volume":"2","author":"V Jackson-Lewis","year":"2007","unstructured":"Jackson-Lewis V, Przedborski S . Protocol for the MPTP mouse model of Parkinson's disease. Nat Protoc 2007; 2: 141\u2013151.","journal-title":"Nat Protoc"}],"container-title":["Cell Death & Differentiation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/cdd2015135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cdd2015135","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cdd2015135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:08:33Z","timestamp":1684415313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cdd2015135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,30]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["BFcdd2015135"],"URL":"https:\/\/doi.org\/10.1038\/cdd.2015.135","relation":{},"ISSN":["1350-9047","1476-5403"],"issn-type":[{"value":"1350-9047","type":"print"},{"value":"1476-5403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,30]]},"assertion":[{"value":"15 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}