| http://purl.uniprot.org/citations/11943812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11943812 | http://www.w3.org/2000/01/rdf-schema#comment | "The alpha-synuclein gene is implicated in the pathogenesis of Parkinson's disease. Although alpha-synuclein function is uncertain, the protein has homology to the chaperone molecule 14-3-3. In addition, alpha-synuclein can bind to 14-3-3, and both alpha-synuclein and 14-3-3 bind to many of the same proteins. Because 14-3-3 binds to and activates tyrosine hydroxylase, the rate-limiting enzyme in dopamine (DA) biosynthesis, we explored whether alpha-synuclein also bound to tyrosine hydroxylase and influenced its activity. Immunoprecipitation revealed an interaction between alpha-synuclein and tyrosine hydroxylase in brain homogenates and MN9D dopaminergic cells. Colocalization of alpha-synuclein with tyrosine hydroxylase was confirmed by immunoelectron microscopy. To explore the consequences of the interaction, we measured the effect of recombinant alpha-synuclein on tyrosine hydroxylase activity in a cell-free system and observed a dose-dependent inhibition of tyrosine hydroxylase by alpha-synuclein. To measure the impact of alpha-synuclein on tyrosine hydroxylase in dopaminergic cells, we stably transfected MN9D cells with wild-type or A53T mutant alpha-synuclein. Overexpression of wild-type or A53T mutant alpha-synuclein did not significantly alter tyrosine hydroxylase protein levels in our stably transfected cells. However, overexpressing cell lines had significantly reduced tyrosine hydroxylase activity and a corresponding reduction in dopamine synthesis. The reduction in cellular dopamine levels was not caused by increased dopamine catabolism or dopamine efflux. These data suggest that alpha-synuclein plays a role in the regulation of dopamine biosynthesis, acting to reduce the activity of tyrosine hydroxylase. If so, a loss of soluble alpha-synuclein, by reduced expression or aggregation, could increase dopamine synthesis with an accompanying increase in reactive dopamine metabolites."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.22-08-03090.2002"xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/author | "Guo F."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/author | "Waymire J.C."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/author | "Perez R.G."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/author | "Liu J.J."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/author | "Lin E."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/author | "Zigmond M.J."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/pages | "3090-3099"xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/title | "A role for alpha-synuclein in the regulation of dopamine biosynthesis."xsd:string |
| http://purl.uniprot.org/citations/11943812 | http://purl.uniprot.org/core/volume | "22"xsd:string |
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