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)

Duchenne's dystrophy (DMD), a recessive chromosome X-related disease, is the most common and severe form of myopathy. The different theories (vascular, neurogenic, membraneous, calcic and auto-immune) formulated to account for this disease have not been swept away by the discovery of the DMD gene and the deficient protein, dystrophin, since the exact cellular role played by the latter is still unknown. Our work on skeletal muscle has demonstrated a mitochondrial deficiency of the calcium-specific protein, calmitine, in degenerating muscle of myopathic persons and animals. Considering its great affinity for calcium, this protein specific to skeletal muscle could be essential to mitochondrial calcium regulation and thus to the functioning of the entire muscle cell. Its deficiency in Duchenne's and Becker type muscular dystrophy could be due to a mitochondrial genome alteration solely accountable for muscular degeneration. This hypothesis challenges the supposedly essential but still undefined role that researchers have attributed to dystrophin.
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PMID:Muscular degeneration in Duchenne's dystrophy may be caused by a mitochondrial defect. 766 33

We compared the myotoxic effect of chlorpromazine on mitochondria of gastrocnemius muscle in X-related muscular dystrophy (mdx) and control mice relative to changes in calmitine and calcium concentrations before and 3 and 6 days after a single injection of the drug. The results indicate that mdx mouse mitochondria are less sensitive to the myotoxic effect of chlorpromazine; calmitine and calcium binding were only slightly reduced compared to controls. Our observations indicate that the calmitine structure could differ in mdx and control mice with respect to calcium binding structures, and that the presence of calmitine in the mitochondria of mdx mouse skeletal muscle could explain why muscle degeneration does not occur in these animals. However, the muscles of patients with Duchenne muscular dystrophy (DMD) are lacking in calmitine and are subject to extensive progressive degeneration.
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PMID:Mdx mouse skeletal muscle: could a mitochondrial factor be responsible for the absence of progressive necrosis? 804 1

We studied the effect of mitochondrial extracts of skeletal muscle obtained from patients with Duchenne's muscular dystrophy (DMD) on calmitine of the mitochondrial matrix isolated from skeletal muscle of control mice. Our results in vitro clearly show that calmitine of the mitochondrial matrix of control muscle was degraded in the presence of mitochondrial extracts of muscle from DMD patients. The diseased muscle apparently contains an abnormal calmitine-specific proteolytic factor responsible for the calmitine deficiency previously observed in this tissue. As calmitine binds calcium and probably plays a role in regulating the balance of bound and free calcium within mitochondria, a calmitine deficiency could result in an overload of mitochondrial free calcium. Certain enzymes involved in ATP synthesis would be inhibited, resulting in the muscular degeneration characteristic of this myopathy. Our results suggest the cause of mitochondrial calcium overload and the events leading to muscular degeneration in this disease model. Abnormal protease activity could be the factor triggering all of these processes in the DMD patient. These findings suggest that it may now feasible to search for an efficient pharmacologic treatment for DMD.
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PMID:Skeletal muscle of patients with Duchenne's muscular dystrophy: evidence of a mitochondrial proteolytic factor responsible for calmitine deficiency. 866 Mar 74

We studied the effect of mitochondrial extracts from skeletal muscle of patients with Duchenne's muscular dystrophy (DMD) on calmitine from the skeletal muscle of normal mice and control subjects. Our results clearly show the existence of an abnormal proteolytic activity of mitochondria from patients with DMD on calmitine from the normal mouse. This proteolytic activity was not found on calmitine from the control subject. Overall, our observations suggest that calmitine concentration in the muscle of the control subject remains elevated because of the presence of a calmitine-specific protease and an inhibitor of this protease which regulates and/or suppresses the activity of the enzyme according to the requirements of the muscle cell. Conversely, the calmitine deficiency observed in the muscle of patients with DMD would be due to the absence of this inhibitor. This would account for the continual activity of the enzyme in degrading calmitine as soon as it is synthesized. The identification of this inhibitor is currently being investigated in our laboratory.
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PMID:Absence of a calmitine-specific protease inhibitor in skeletal muscle mitochondria of patients with Duchenne's muscular dystrophy. 878 Jun 77

This study demonstrates that the cause of calmitine deficiency in dy/dy dystrophic mice and patients with Duchenne's muscular dystrophy (DMD) is the same; i.e., the absence of an inhibitor of calmitine-specific mitochondrial protease. This inhibitor, which is present in control mice and control subjects, prevented degradation of the protein. It is also shown that a drug (IP96) was capable in vitro of inhibiting calmitine-specific mitochondrial protease from muscle of DMD patients and dy/dy mice. This drug was also active in vivo in an experimental model of myopathy created in the normal mouse by a single injection of chlorpromazine, a myotoxic drug, which induced temporary calmitine degradation. Thus, it seems quite likely that IP96 prevents calmitine degradation by inhibiting the specific protease.
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PMID:A drug inhibits the mitochondrial protease inducing calmitine deficiency in skeletal muscle of patients with Duchenne's muscular dystrophy and dy/dy dystrophic mice. 912 22