| http://purl.uniprot.org/citations/35617426 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35617426 | http://www.w3.org/2000/01/rdf-schema#comment | "Fragile X–associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative disease in premutation carriers of the expanded CGG repeat in FMR1 that presents with a spectrum of neurological manifestations, such as gait ataxia, intention tremor, and parkinsonism [P. J. Hagerman, R. J. Hagerman, Ann. N. Y. Acad. Sci. 1338, 58–70 (2015); S. Jacquemont et al., JAMA 291, 460–469 (2004)]. Here, we performed whole-genome sequencing (WGS) on male premutation carriers (CGG55–200) and prioritized candidate variants to screen for candidate genetic modifiers using a Drosophila model of FXTAS. We found 18 genes that genetically modulate CGG-associated neurotoxicity in Drosophila, such as Prosbeta5 (PSMB5), pAbp (PABPC1L), e(y)1 (TAF9), and CG14231 (OSGEPL1). Among them, knockdown of Prosbeta5 (PSMB5) suppressed CGG-associated neurodegeneration in the fly as well as in N2A cells. Interestingly, an expression quantitative trait locus variant in PSMB5, PSMB5rs11543947-A, was found to be associated with decreased expression of PSMB5 and delayed onset of FXTAS in human FMR1 premutation carriers. Finally, we demonstrate evidence that PSMB5 knockdown results in suppression of CGG neurotoxicity via both the RAN translation and RNA-mediated toxicity mechanisms, thereby presenting a therapeutic strategy for FXTAS."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2118124119"xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Cao Y."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Guo X."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Huang Y."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Gu Y."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Johnston R."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Lim J."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Nelson D.L."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Kang Y."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Jin P."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Todd P.K."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Zwick M.E."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Qin Z."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Juncos J."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Warren S.T."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Epstein M.P."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Cutler D.J."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Sherman S.L."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Kong H.E."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Allen E.G."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Malik I."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Wingo T.S."xsd:string |
| http://purl.uniprot.org/citations/35617426 | http://purl.uniprot.org/core/author | "Shubeck L."xsd:string |