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, SW
dc.contributor.author Dunlop, RA
dc.contributor.author Rowe, A
dc.contributor.author Double, KL
dc.contributor.author Rodgers, KJ
dc.date.accessioned 2012-10-12T03:34:25Z
dc.date.issued 2012-11
dc.identifier.citation Experimental Neurology, 2012, 238 (1), pp. 29 - 37
dc.identifier.issn 0014-4886
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. © 2011 Elsevier Inc.
dc.language eng
dc.relation.isbasedon 10.1016/j.expneurol.2011.09.029
dc.title L-DOPA is incorporated into brain proteins of patients treated for Parkinson's disease, inducing toxicity in human neuroblastoma cells in vitro
dc.type Journal Article
dc.description.version Published
dc.parent Experimental Neurology
dc.journal.volume 1
dc.journal.volume 238
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 1103 Clinical Sciences
dc.personcode 111642
dc.personcode 115899
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 Incorporation
dc.description.keywords L-DOPA
dc.description.keywords L-tyrosine
dc.description.keywords Parkinson's disease
dc.description.keywords Protein
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true
utslib.collection.history Closed (ID: 3)
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)


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