2007
DOI: 10.1172/jci30556
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Interplay of IKK/NF-κB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy

Abstract: Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder associated with dystrophin deficiency that results in chronic inflammation and severe skeletal muscle degeneration. In DMD mouse models and patients, we find that IκB kinase/NF-κB (IKK/NF-κB) signaling is persistently elevated in immune cells and regenerative muscle fibers. Ablation of 1 allele of the p65 subunit of NF-κB was sufficient to improve pathology in mdx mice, a model of DMD. In addition, conditional deletion of IKKβ in mdx mice elucidat… Show more

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Cited by 385 publications
(521 citation statements)
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“…Although this disease is caused primarily by a mutation in the gene encoding dystrophin 46 , several genes slow disease progression in mdx mice [47][48][49][50] . Thus, therapeutic strategies may not be limited to those directly targeting the dystrophin gene.…”
Section: Discussionmentioning
confidence: 99%
“…Although this disease is caused primarily by a mutation in the gene encoding dystrophin 46 , several genes slow disease progression in mdx mice [47][48][49][50] . Thus, therapeutic strategies may not be limited to those directly targeting the dystrophin gene.…”
Section: Discussionmentioning
confidence: 99%
“…Recently, blocking IKKb has been considered as a potential approach for anti-chronic inflammation in dystrophic muscles by targeting the upstream activator of the classical NF-kB pathway. The peptide inhibitor of IKKb, 9 for example, reduced inflammation and necrosis while enhancing regeneration. However, these approaches require repeated treatments and have the potential for systemic side effects.…”
Section: Discussionmentioning
confidence: 99%
“…9,32 Hence, we attempted to silence the p65 gene to improve the pathologies observed in mdx mice. Our findings indicate that AAV-based p65-shRNA has the capacity to decrease immune cell infiltration, to inhibit necrosis and to protect the myofiber membranes.…”
Section: Discussionmentioning
confidence: 99%
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