| Peracetylated N-acetylmannosamine, a synthetic sugar molecule, effectively rescues muscle phenotype and biochemical defects in a mouse model of sialic acid deficient myopathy. | |
| | |
MedLine Citation:
|
PMID: 22157763 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy (DMRV/hIBM), characterized by progressive muscle atrophy, weakness and degeneration, is due to mutations in GNE, a gene encoding a bifunctional enzyme critical in sialic acid biosynthesis. In the DMRV/hIBM mouse model, which exhibited hyposialylation in various tissue in addition to muscle atrophy, weakness, and degeneration, we recently have demonstrated that the myopathic phenotype was prevented by oral administration of N-acetylneuraminic acid, N-acetylmannosamine and sialyllactose, underscoring the crucial role of hyposialylation in disease pathomechanism. The choice for the preferred molecule, however, was limited probably by the complex pharmacokinetics of sialic acids, and the lack of biomarkers which could clearly show dose-response. To address these issues, we screened several synthetic sugar compounds that could increase sialylation more remarkably and allow demonstration of measurable effects in the DMRV/hIBM mice. In this study, we found that tetra-O-acetylated ManNAc (Ac4ManNAc) increased cell sialylation most efficiently, and in vivo evaluation in DMRV/hIBM mice revealed more dramatic, measurable effect and improvement in muscle phenotype, enabling us to establish analysis of protein biomarkers that can be used for assessing response to treatment. Our results provide a proof of concept in sialic acid-related molecular therapy with synthetic monosaccharides. |
| | |
Authors:
|
May Christine V Malicdan; Satoru Noguchi; Tomoharu Tokutomi; Yu-Ichi Goto; Ikuya Nonaka; Yukiko K Hayashi; Ichizo Nishino |
Related Documents
:
|
22055963 - Isolation and partial characterisation of bovine rumen myosin. 7148733 - Carbohydrate malabsorption in infants with rotavirus diarrhea. 1856193 - Determination of disulfide bond pairs and stability in recombinant tick anticoagulant p... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-8 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
National Institute of Neuroscience, NCNP, Japan; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mitochondrial Rac1 import and electron transfer from cytochrome c is required for pulmonary fibrosis...
Next Document: The enzymatic activity of lysyl oxidase like-2 (LOXL2) is not required for LOXL2 induced inhibition ...