ReferenceID 458
Ribitol restores functionally glycosylated α-dystroglycan and improves muscle function in dystrophic FKRP-mutant mice
Nat Commun
O-mannosylated α-dystroglycan (α-DG) serves as receptors for cell-cell and cell-extracellular matrix adhesion and signaling. Hypoglycosylation of α-DG is involved in cancer progression and underlies dystroglycanopathy wi
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Record Fields
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- Reference Id
- 458
- Evidence Id
- 17048
- Core Evidence Id
- 17048
- Source Reference Id
- 1145
- Herb2 Reference Id
- HBREF001931
- Subject Paper Key
- HBIN048522_30150693
- Pubmed Id
- 30150693
- Doi
- 10.1038/s41467-018-05990-z
- Paper Title
- Ribitol restores functionally glycosylated α-dystroglycan and improves muscle function in dystrophic FKRP-mutant mice
- Paper Abstract
- O-mannosylated α-dystroglycan (α-DG) serves as receptors for cell-cell and cell-extracellular matrix adhesion and signaling. Hypoglycosylation of α-DG is involved in cancer progression and underlies dystroglycanopathy with aberrant neuronal development. Here we report that ribitol, a pentose alcohol with previously unknown function in mammalian cells, partially restores functional O-mannosylation of α-DG (F-α-DG) in the dystroglycanopathy model containing a P448L mutation in fukutin-related protein (FKRP) gene, which is clinically associated with severe congenital muscular dystrophy. Oral administration of ribitol increases levels of ribitol-5-phosphate and CDP-ribitol and restores therapeutic levels of F-α-DG in skeletal and cardiac muscles. Furthermore, ribitol, given before and after the onset of disease phenotype, reduces skeletal muscle pathology, significantly decreases cardiac fibrosis and improves skeletal and respiratory functions in the FKRP mutant mice. Ribitol treatment presents a new class, low risk, and easy to administer experimental therapy to restore F-α-DG in FKRP-related muscular dystrophy.
- Journal
- Nat Commun
- Publish Year
- 2018
- Experiment Subject
- fkrp-deficient mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Muscular Dystrophy
- Paper Title Cn
- Paper Title En
- Ribitol restores functionally glycosylated α-dystroglycan and improves muscle function in dystrophic FKRP-mutant mice
- Bilingual Status
- semi_complete