| http://purl.uniprot.org/citations/32749068 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32749068 | http://www.w3.org/2000/01/rdf-schema#comment | "How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin-remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging-dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down-regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α-synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down-regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD-associated gene)-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age-related disorders including PD."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.org/dc/terms/identifier | "doi:10.1111/acel.13210"xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Chen F."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Chen W."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Huang K."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Ren Y."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Sun L."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Zhang Z."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Yang H."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Yang M."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Xie S."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Ye M."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Yao Y."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Yan Z."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Chen K."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Xiao M."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Ma F."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Haque M.E."xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Zhang X.'"xsd:string |
| http://purl.uniprot.org/citations/32749068 | http://purl.uniprot.org/core/author | "Zhou H.M."xsd:string |