This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective: To identify stage-specific induction of molecular pathology pathways in Duchenne muscular dystrophy (DMD).
Methods: We performed mRNA profiling using muscles from fetopsies, infants (aged 8 to 10 months), and symptomatic patients (aged 5 to 12 years) with DMD, and age- and sex-matched controls. We performed immunohistochemistry to determine changes at the protein level and protein localization.
Results: Activated tissue dendritic cells, expression of toll-like receptor 7, and strong induction of nuclear factor-κB pathways occurred soon after birth in DMD muscle. Two muscle wasting pathways, atrogin-1 and myostatin, were not induced at any stage of the disease. Normal muscle showed accumulation of glycolytic and oxidative metabolism capacity with increased age, but this accumulation failed in DMD. The transforming growth factor (TGF)-β pathway was strongly induced in symptomatic patients, with expression of TGFβ type II receptor and apoptosis signal-regulating kinase 1 proteins on subsets of mature DMD myofibers
Conclusions: Our data show stage-specific remodeling of human dystrophin-deficient muscle, with inflammatory pathways predominating in the presymptomatic stages and acute activation of TGFβ and failure of metabolic pathways later in the disease.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Disputes & Debates: Rapid online correspondence
NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
- Stay timely. Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- 200 words maximum.
- 5 references maximum. Reference 1 must be the article on which you are commenting.
- 5 authors maximum. Exception: replies can include all original authors of the article.
- Submitted comments are subject to editing and editor review prior to posting.