Journal article
P.1.13 Autophagy and the pathogenesis of congenital muscular dystrophies
Neuromuscular disorders : NMD, Vol.23(9-10), pp.745-745
10/2013
DOI: 10.1016/j.nmd.2013.06.397
Abstract
Congenital muscular dystrophies are childhood-onset muscle diseases characterized by weakness, significant disabilities and early mortality. In general, CMDs are caused by mutations in genes associated with the dystrophin-associated transmembrane complex. Their primary pathomechanism is likely contraction-induced muscle cell injury due to impaired membrane anchorage. In addition, abnormalities in downstream pathways have been described in experimental models of CMDs. One such pathway is autophagy, an essential intracellular process responsible for removing damaged organelles and long-lived proteins. Altered autophagy has been observed in several disorders, and improving autophagy is proposed as a therapeutic consideration for a broad range of diseases. The overarching goal of this research is to identify new therapeutic strategies for CMDs, and autophagy is an attractive potential target, as well studied, FDA approved drugs exist that modulate its activity. The specific goals of this study are to establish the relationship between CMD disease pathogenesis and autophagy and to determine the impact of modulating autophagy on CMD disease progression. We predict that aberrant autophagy is a common feature of CMDs and that interventions that improve autophagy can reverse aspects of disease pathology and improve overall disease outcome. To accomplish these goals and test these hypotheses, we have used a combined approach of study of biopsy material from patients with CMDs and utilization of zebrafish models of disease. We have determined the burden of aberrant autophagy in CMD biopsies as compared to other congenital muscle diseases. We have also tested the ability of both genetic manipulations and specific drugs that modulate autophagy to alter the CMD phenotype in our zebrafish models. In total, we present data that comprehensively examines the role of autophagy in CMDs and evaluates the potential of altering autophagy as a therapeutic modality.
Details
- Title: Subtitle
- P.1.13 Autophagy and the pathogenesis of congenital muscular dystrophies
- Creators
- E Horstick - University of MichiganX Li - University of MichiganS Moore - University of IowaJ.J Dowling - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Neuromuscular disorders : NMD, Vol.23(9-10), pp.745-745
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.nmd.2013.06.397
- ISSN
- 0960-8966
- eISSN
- 1873-2364
- Language
- English
- Date published
- 10/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984201419902771
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