Peptide-Based Inhibition of NF-κB Rescues Diaphragm Muscle Contractile Dysfunction in a Murine Model of Duchenne Muscular Dystrophy
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Deterioration of diaphragm function is one of the prominent factors that contributes to the susceptibility of serious respiratory infections and development of respiratory failure in patients with Duchenne Muscular Dystrophy (DMD). The NF-κB signaling pathway has been implicated as a contributing factor of dystrophic pathology, making it a potential therapeutic target. Previously, we demonstrated that pharmacological inhibition of NF-κB via a small NEMO Binding Domain (NBD) peptide was beneficial for reducing pathological features of mdx mice. Now, we stringently test the effectiveness and clinical potential of NBD by treating mdx mice with various formulations of NBD and use diaphragm function as our primary outcome criteria. We found that administering DMSO-soluble NBD rescued 78% of the contractile deficit between mdx and wild-type (WT) diaphragm. Interestingly, synthesis of a GLP NBD peptide as an acetate salt permitted its solubility in water, but as a negative consequence, also greatly attenuated functional efficacy. However, replacing the acetic acid counterion of the NBD peptide with trifluoroacetic acid retained the peptide's water solubility and significantly restored mdx diaphragm contractile function and improved histopathological indices of disease in both diaphragm and limb muscle. Together, these results support the feasibility of using a mass-produced, water-soluble NBD peptide for clinical use.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Peptide-Based Inhibition of NF-κB Rescues Diaphragm Muscle Contractile Dysfunction in a Murine Model of Duchenne Muscular Dystrophy
- Date Crossref
- 20/01/2011
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
The Ohio State University Department of Molecular Virology pays non établi dans la noticeUniversité ou école supérieure
-
University of North Carolina at Chapel Hill Department of Pathology and Laboratory Medicine pays non établi dans la noticeUniversité ou école supérieure
-
Nationwide Children's Hospital pays non établi dans la noticeÉtablissement de santé
-
University of Pittsburgh Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
-
Veterans Health Administration pays non établi dans la noticeOrganisme public
-
Nationwide Children’s Research Institute pays non établi dans la noticeStructure de recherche
-
Department of Veterans Affairs Medical Center pays non établi dans la noticeÉtablissement de santé
Department of Molecular Virology — The Ohio State University, Department of Pathology and Laboratory Medicine — University of North Carolina at Chapel Hill et Nationwide Children's Hospital, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.