| http://purl.uniprot.org/citations/35422047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35422047 | http://www.w3.org/2000/01/rdf-schema#comment | "Ribitol-phosphate modification is crucial for the functional maturation of α-dystroglycan. Its dysfunction is associated with muscular dystrophy, cardiomyopathy, and central nervous system abnormalities; however, no effective treatments are currently available for diseases caused by ribitol-phosphate defects. In this study, we demonstrate that prodrug treatments can ameliorate muscular dystrophy caused by defects in isoprenoid synthase domain containing (ISPD), which encodes an enzyme that synthesizes CDP-ribitol, a donor substrate for ribitol-phosphate modification. We generated skeletal muscle-selective Ispd conditional knockout mice, leading to a pathogenic reduction in CDP-ribitol levels, abnormal glycosylation of α-dystroglycan, and severe muscular dystrophy. Adeno-associated virus-mediated gene replacement experiments suggested that the recovery of CDP-ribitol levels rescues the ISPD-deficient pathology. As a prodrug treatment strategy, we developed a series of membrane-permeable CDP-ribitol derivatives, among which tetraacetylated CDP-ribitol ameliorated the dystrophic pathology. In addition, the prodrug successfully rescued abnormal α-dystroglycan glycosylation in patient fibroblasts. Consequently, our findings provide proof-of-concept for supplementation therapy with CDP-ribitol and could accelerate the development of therapeutic agents for muscular dystrophy and other diseases caused by glycosylation defects."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-022-29473-4"xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Endo T."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Matsumoto R."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Okada T."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Kobayashi K."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Manya H."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Nakashima H."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Toda T."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Masuda C."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Hoshino S."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Lefeber D.J."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Kanagawa M."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Imae R."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/author | "Tokuoka H."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/name | "Nat Commun"xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/pages | "1847"xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/title | "CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model."xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://purl.uniprot.org/core/volume | "13"xsd:string |
| http://purl.uniprot.org/citations/35422047 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35422047 |
| http://purl.uniprot.org/citations/35422047 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35422047 |
| http://purl.uniprot.org/uniprot/#_A0A1Y7VK76-mappedCitation-35422047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35422047 |
| http://purl.uniprot.org/uniprot/#_A0A1Y7VM96-mappedCitation-35422047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35422047 |