L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro

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dc.contributor.author Chan, Sandra en_US
dc.contributor.author Dunlop, Rachael en_US
dc.contributor.author Rowe, Anthony en_US
dc.contributor.author Double, Kay en_US
dc.contributor.author Rodgers, Kenneth en_US
dc.contributor.editor en_US
dc.date.accessioned 2012-10-12T03:34:25Z
dc.date.available 2012-10-12T03:34:25Z
dc.date.issued 2012 en_US
dc.identifier 2011000545 en_US
dc.identifier.citation Chan Sandra et al. 2012, 'L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro', Academic Press, vol. 238, no. 1, pp. 29-37. en_US
dc.identifier.issn 0014-4886 en_US
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/18612
dc.description.abstract Levodopa (l-dopa), a close structural analogue of the protein amino acid l-tyrosine, can substitute for l-tyrosine in protein synthesis and be mistakenly incorporated into newly synthesised proteins in vitro. We show that l-dopa-containing proteins are present in the brain in l-DOPA-treated Parkinson's disease patients and accumulate in specific brain regions. In vitro studies demonstrate that substitution of l-tyrosine residues in proteins with l-DOPA causes protein misfolding and promotes protein aggregation in SH-SY5Y neuroblastoma cells resulting in the appearance of autofluorescent bodies. We show that the presence of l-DOPA-containing proteins causes profound changes in mitochondria and stimulates the formation of autophagic vacuoles in cells. Unlike l-DOPA, which is toxic to cells through its ability to generate radicals, proteins containing incorporated l-DOPA are toxic to SH-SY5Y cells by a mechanism independent of oxidative stress and resistant to antioxidants. These data suggest that the accumulation of l-DOPA-containing proteins in vulnerable cells might negatively impact on cell function. en_US
dc.language en_US
dc.publisher Academic Press en_US
dc.relation.isbasedon http://dx.doi.org/10.1016/j.expneurol.2011.09.029 en_US
dc.title L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro en_US
dc.parent Experimental Neurology en_US
dc.journal.volume 238 en_US
dc.journal.number 1 en_US
dc.publocation United States en_US
dc.identifier.startpage 29 en_US
dc.identifier.endpage 37 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 110300 en_US
dc.personcode 0000082809 en_US
dc.personcode 115899 en_US
dc.personcode 0000082810 en_US
dc.personcode 0000082811 en_US
dc.personcode 111642 en_US
dc.percentage 100 en_US
dc.classification.name Clinical Sciences en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords l-DOPA; Protein; Incorporation; Parkinson's disease; l-tyrosine en_US
dc.staffid 111642 en_US


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