| http://purl.uniprot.org/citations/27736935 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27736935 | http://www.w3.org/2000/01/rdf-schema#comment | "We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson's disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo. In S. cerevisiae, the co-occurrence of low PE and α-syn in psd1Δ cells triggers mitochondrial defects, stress in the endoplasmic reticulum, misprocessing of glycosylphosphatidylinositol-anchored proteins, and a 3-fold increase in the level of α-syn. The goal of this study was to identify drugs that rescue this phenotype. We screened the Prestwick library of 1121 Food and Drug Administration-approved drugs using psd1Δ + α-syn cells and identified cyclosporin A, meclofenoxate hydrochloride, and sulfaphenazole as putative protective compounds. The protective activity of these drugs was corroborated using C. elegans in which α-syn is expressed specifically in the dopaminergic neurons, with psd-1 depleted by RNAi. Worm populations were examined for dopaminergic neuron survival following psd-1 knockdown. Exposure to cyclosporine, meclofenoxate, and sulfaphenazole significantly enhanced survival at day 7 in α-syn-expressing worm populations whereby 50-55% of the populations displayed normal neurons, compared to only 10-15% of untreated animals. We also found that all three drugs rescued worms expressing α-syn in dopaminergic neurons that were deficient in the phospholipid cardiolipin following cardiolipin synthase (crls-1) depletion by RNAi. We discuss how these drugs might block α-syn pathology in dopaminergic neurons."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0164465"xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Barron A."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Lee Y.J."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Patel D."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Wang S."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Zhang S."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Xu C."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Caldwell G.A."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Caldwell K.A."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Witt S.N."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/author | "Galiano F."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/pages | "e0164465"xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/title | "Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson's Disease."xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://purl.uniprot.org/core/volume | "11"xsd:string |
| http://purl.uniprot.org/citations/27736935 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27736935 |
| http://purl.uniprot.org/citations/27736935 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27736935 |
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| http://purl.uniprot.org/uniprot/#_Q10949-mappedCitation-27736935 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27736935 |
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| http://purl.uniprot.org/uniprot/Q10949 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/27736935 |