1. Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner
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Ji-Min Park, Dong-Hwan Ho, Hye Jin Yun, Hye-Jung Kim, Chan Hong Lee, Sung Woo Park, Young Hoon Kim, Ilhong Son, and Wongi Seol
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α-Synuclein ,Dexamethasone ,Glucocorticoid receptor(GR) ,LRRK2 ,Parkinson’s disease ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
LRRK2 (leucine-rich repeat kinase 2) has been identified as agene corresponding to PARK8, an autosomal-dominant genefor familial Parkinson’s disease (PD). LRRK2 pathogenicspecificmutants induce neurotoxicity and shorten neurites. Toelucidate the mechanism underlying LRRK2 expression, weconstructed the LRRK2-promoter-luciferase reporter and used itfor promoter analysis. We found that the glucocorticoid receptor(GR) transactivated LRRK2 in a ligand-dependent manner.Using quantitative RT-PCR and Western analysis, we furthershowed that treatment with dexamethasone, a synthetic GRligand, induced LRRK2 expression at both the transcriptionaland translational levels, in dopaminergic MN9D cells. Dexamethasonetreatment also increased expression of α-synuclein,another PD causative gene, and enhanced transactivation ofthe α-synuclein promoter-luciferase reporter. In addition, dexamethasonetreatment to MN9D cells weakly induced cytotoxicitybased on an LDH assay. Because glucocorticoidhormones are secreted in response to stress, our data suggestthat stress might be a related factor in the pathogenesis of PD.[BMB Reports 2013; 46(9): 454-459]
- Published
- 2013
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