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)

There have been few reports of congenital inflammatory myopathy in the literature, and most of these have been associated with congenital muscular dystrophy. We review the literature and present a case with electromyographic and muscle biopsy evidence of congenital inflammatory myopathy with onset in the perinatal period and no evidence of a congenital muscular dystrophy. There was evidence of subjective improvement following corticosteroid administration (approximately 1 mg/kg per day) with a concomitant normalization of the serum creatine kinase activity. Of particular interest in the case was the history of maternal infection, suggesting a possible postinfectious molecular mimicry as the etiology of the muscle inflammation. This case suggests that a rare form of congenital inflammatory myopathy does exist that is not associated with a congenital muscular dystrophy. A preliminary classification scheme is proposed to separate true congenital cases from those acquired after birth and those cases associated with congenital dystrophy.
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PMID:Congenital inflammatory myopathy: a demonstrative case and proposed diagnostic classification. 1187 Jun 95

Several lines of evidence indicate that the nonenzymatic oxidative modification of proteins and the subsequent accumulation of the modified proteins have been found in cells during aging and oxidative stress and in various pathological states, including premature diseases, muscular dystrophy, rheumatoid arthritis, and atherosclerosis. Our previous work suggested the existence of molecular mimicry between antibodies raised against hydroxy-2-nonenal (HNE)-modified protein and anti-DNA autoantibodies, a serologic hallmark of systemic lupus erythematosus (SLE). In the present study, we investigated the possible involvement of HNE-modified proteins as the endogenous source of the anti-DNA antibodies. Accumulation of the antigen recognized by the antibody against the HNE-modified protein was observed in the nucleus of almost all of the epidermal cells from patients with autoimmune diseases, including SLE. The SLE patients also showed significantly higher serum levels of the anti-HNE titer than healthy individuals. To determine if a specific anti-DNA response could be initiated by the HNE-derived epitopes, we immunized BALB/c mice with the HNE-modified protein and observed a progressive increase in the anti-DNA response. Moreover, we generated the monoclonal antibodies, showing recognition specificity toward DNA, and found that they can bind to two structurally distinct antigens (i.e. the native DNA and protein-bound 4-oxo-2-nonenal). The findings in this study provide evidence to suspect an etiologic role for lipid peroxidation in autoimmune diseases.
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PMID:Protein-bound 4-hydroxy-2-nonenal: an endogenous triggering antigen of antI-DNA response. 1758 42

RNA is an important yet vastly underexploited target for small molecule chemical probes or lead therapeutics. Small molecules have been used successfully to modulate the function of the bacterial ribosome, viral RNAs and riboswitches. These RNAs are either highly expressed or can be targeted using substrate mimicry, a mainstay in the design of enzyme inhibitors. However, most cellular RNAs are neither highly expressed nor have a lead small molecule inhibitor, a significant challenge for drug discovery efforts. Herein, I describe the design of small molecules targeting expanded repeating transcripts that cause myotonic muscular dystrophy (DM). These test cases illustrate the challenges of designing small molecules that target RNA and the advantages of targeting repeating transcripts. Lastly, I discuss how small molecules might be more advantageous than oligonucleotides for targeting RNA.
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PMID:Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts. 2393 37

This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.
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PMID:Mitochondrial dysfunction in neuromuscular disorders. 2433 62