Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in dystrophin cause muscular dystrophy but also affect the CNS, including information processing in the retina. To better understand the molecular basis of these CNS deficits, we analyzed the molecular composition and developmental appearance of dystrophin and of the dystrophin-associated protein complex (DPC) in the embryonic and adult avian retina. We detected a concentration of the DPC at the vitreal border and in the outer plexiform layer of the adult retina. At both locations the complex had a different molecular composition and different developmental expression pattern. At the vitreal border, the complex was composed of utrophin, alpha-dystrobrevin-1, and dystroglycan, and was present at all stages of retinal development even before neurogenesis and gliogenesis. On the other hand, the complex in the outer plexiform layer consisted of dystrophin, beta-dystrobrevin and dystroglycan. The distribution of this complex changed from a diffusely distributed to an aggregated form during development concomitant with synapse formation in the outer plexiform layer. Solubilization of the retinal extracellular matrix by intravitreal injection of collagenase resulted in a redistribution of the complex at the retinal vitreal border but had no influence on the distribution of the dystrophin-associated proteins in the outer plexiform layer. These results demonstrate two types of dystrophin-like complexes in the chick retina with differential molecular compositions, different anchorage to the extracellular matrix, and different developmental expression patterns, suggesting distinct functions for the DPC at both locations.
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PMID:Molecular diversity of the dystrophin-like protein complex in the developing and adult avian retina. 1198 13

Objective Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy (PMD). Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), congenital muscular dystrophy (CMD) by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.
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PMID:Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy. 1768 3

To identify serum biomarkers that allow monitoring of disease progression and treatment effects in Duchenne muscular dystrophy (DMD) patients, levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and osteopontin (OPN) were determined in 63 DMD patients on corticosteroid therapy. These proteins were selected for their role in the pathogenesis of muscular dystrophy. Levels of MMP-9 and TIMP-1 were significantly higher in sera of DMD patients compared to healthy controls, whereas the OPN levels showed no significant difference. MMP-9 levels were also observed to be significantly higher in older, nonambulant patients, compared to ambulant patients. Longitudinal data from a smaller cohort of DMD patients followed up for over 4years showed that MMP-9, but not TIMP-1 increased significantly with age. Hence, MMP-9 is a potential DMD biomarker for disease progression. Future studies have to confirm whether serum MMP-9 levels can be used to monitor therapeutic response.
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PMID:Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease progression in Duchenne muscular dystrophy (DMD). 2579 39