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http://purl.uniprot.org/citations/24832624http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24832624http://www.w3.org/2000/01/rdf-schema#comment"Parkinson's disease (PD) is a common neurodegenerative disease, but its pathogenesis remains elusive. A mutation in ubiquitin C-terminal hydrolase L1 (UCH-L1) is responsible for a form of genetic PD which strongly resembles the idiopathic PD. We previously showed that 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4'DHBnTIQ) is an endogenous parkinsonism-inducing dopamine derivative. Here, we investigated the interaction between 3',4'DHBnTIQ and UCH-L1 and its possible role in the pathogenesis of idiopathic PD. Our results indicate that 3',4'DHBnTIQ binds to UCH-L1 specifically at Cys152 in vitro. In addition, 3',4'DHBnTIQ treatment increased the amount of UCH-L1 in the insoluble fraction of SH-SY5Y cells and inhibited its hydrolase activity to 60%, reducing the level of ubiquitin in the soluble fraction of SH-SY5Y cells. Catechol-modified UCH-L1 as well as insoluble UCH-L1 were detected in the midbrain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated PD model mice. Structurally as well as functionally altered UCH-L1 have been detected in the brains of patients with idiopathic PD. We suggest that conjugation of UCH-L1 by neurotoxic endogenous compounds such as 3',4'DHBnTIQ might play a key role in onset and progression of idiopathic PD. We investigated the interaction between ubiquitin C-terminal hydrolase L1 (UCH-L1) and the brain endogenous parkinsonism inducer 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4'DHBnTIQ). Our results indicate that 3',4'DHBnTIQ binds to UCH-L1 specifically at cysteine 152 and induces its aggregation. 3',4'DHBnTIQ also inhibits the hydrolase activity of UCH-L1. Catechol-modified as well as insoluble UCH-L1 were detected in the midbrains of MPTP-treated Parkinson's disease (PD) model mice. Conjugation of UCH-L1 by neurotoxic endogenous compounds like 3',4'DHBnTIQ might play a key role in onset and progression of PD."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.org/dc/terms/identifier"doi:10.1111/jnc.12762"xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Okuda K."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Kotake Y."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Ohta S."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Sakamoto S."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Toyama T."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Kumagai Y."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Contu V.R."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Miyara M."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Sanoh S."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/author"Samizo S."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/name"J Neurochem"xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/pages"826-838"xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/title"Endogenous neurotoxic dopamine derivative covalently binds to Parkinson's disease-associated ubiquitin C-terminal hydrolase L1 and alters its structure and function."xsd:string
http://purl.uniprot.org/citations/24832624http://purl.uniprot.org/core/volume"130"xsd:string
http://purl.uniprot.org/citations/24832624http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24832624
http://purl.uniprot.org/citations/24832624http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24832624
http://purl.uniprot.org/uniprot/#_B2RD14-mappedCitation-24832624http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24832624
http://purl.uniprot.org/uniprot/#_A6NLJ7-mappedCitation-24832624http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24832624
http://purl.uniprot.org/uniprot/#_P09936-mappedCitation-24832624http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24832624
http://purl.uniprot.org/uniprot/#_Q59GS1-mappedCitation-24832624http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24832624
http://purl.uniprot.org/uniprot/#_V9HW74-mappedCitation-24832624http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24832624