Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy is the most common inherited lethal X-linked disorder of mankind and is caused by dystrophin deficiency. The steps involved in the dystrophin-deficiency-induced cascade which lead to myofiber necrosis, progressive muscle wasting in humans and dogs and prominent muscle hypertrophy in mice and cats are obscure. Dystrophin is an intracellular component of the membrane cytoskeleton and its absence would be expected to cause necrosis of isolated myofibers (cell autonomous defect). However, all dystrophin-deficient muscles characteristically show simultaneous degeneration of large groups of muscle fibers (grouped necrosis). This implies that cell death may be mediated by extracellular, non-cell autonomous factors which occur as a secondary consequence of dystrophin deficiency. We have proposed a model where tissue pathology may be mediated by infiltrating mast cells (Gorospe et al., J Neurol Sci 1994). Here we show that intramuscular injections of purified mast cell granules induce widespread myofiber necrosis in dystrophin-deficient mdx mice, but not in normal mice. These data support the hypothesis that dystrophin acts as a plasma membrane stabilizer and that its deficiency renders myofibers more susceptible to damage from mast cell proteases. Moreover, our results support the hypothesis that mast cell degranulation may be a trigger for myofiber death in dystrophin-deficient muscle.
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PMID:Dystrophin-deficient myofibers are vulnerable to mast cell granule-induced necrosis. 798 89

Duchenne muscular dystrophy is a lethal muscle wasting disorder, resulting from mutations in the gene encoding for the skeletal muscle protein dystrophin. The absence of functional dystrophin leaves the muscle membrane vulnerable to damage during contraction. Damage initially occurs as 'tears' in the membrane, this damage can be exacerbated by the inflammatory response leading to myofibre necrosis rather than repair. Mast cells resident within skeletal muscle represent an immediate source of pro-inflammatory cytokines. We hypothesise that blockade of mast cell degranulation would reduce the extent of myofibre necrosis in the mdx mouse. Daily cromolyn injections were performed on young and exercised adult mdx mice and histological analysis confirmed that mast cell degranulation contributes to myofibre necrosis. This research identified high biological variation between individual mdx mice in the severity of the dystrophic pathology, and supported a relationship between extent of muscle damage in adult mdx mice and their individual enthusiasm for voluntary wheel running.
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PMID:Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice. 1679 5

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons which leads to muscular atrophy, paralysis and death in 3-5 years from starting symptoms. This disorder is accompanied by noteworthy spinal inflammation mediated in particular by microglia and mast cells. No effective therapy is available. This report describes the effects of administering the anti-inflammatory agent palmitoylethanolamide in a case of sporadic amyotrophic lateral sclerosis. Palmitoylethanolamide treatment led to an improved clinical picture, as evidenced by electromyographic analysis and pulmonary function. Conceivably, the action of palmitoylethanolamide could result, in part, from its ability to dampen mast cell and microglia activation.
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PMID:Amyotrophic lateral sclerosis treatment with ultramicronized palmitoylethanolamide: a case report. 2299 38