Abstract
Although genetic mutations that are responsible for most of the inherited neuromuscular diseases have been identified, the molecular and cellular mechanisms that cause muscle and nerve depletion are not well understood and therapies are lacking. Histological studies of many neuromuscular diseases indicated that loss of motor-nerve and/or skeletal-muscle function might be due to excessive cell death by apoptosis. Recent studies have confirmed this possibility by showing that pathology in mouse models of amyotrophic lateral sclerosis, congenital muscular dystrophy, oculopharyngeal muscular dystrophy and collagen-VI deficiency, but not Duchenne muscular dystrophy, is significantly ameliorated by genetic or pharmacological interventions that have been designed to inhibit apoptosis. Thus, apoptosis greatly contributes to pathology in mouse models of several neuromuscular diseases, and appropriate anti-apoptosis therapy might therefore be beneficial for the corresponding human diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Agrin / genetics
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Agrin / metabolism
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Amyotrophic Lateral Sclerosis / drug therapy*
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Amyotrophic Lateral Sclerosis / enzymology
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Amyotrophic Lateral Sclerosis / genetics
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Animals
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Anti-Bacterial Agents / pharmacology
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Anti-Bacterial Agents / therapeutic use*
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Apoptosis / genetics*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Clinical Trials as Topic
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Disease Models, Animal
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Doxycycline / pharmacology
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Doxycycline / therapeutic use*
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Gene Expression Regulation / drug effects
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Genetic Therapy* / methods
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Humans
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Laminin / genetics
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Laminin / metabolism
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Mice
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Minocycline / pharmacology
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Minocycline / therapeutic use*
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Muscular Dystrophies / genetics
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Muscular Dystrophies / metabolism
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Muscular Dystrophies / therapy*
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Muscular Dystrophy, Oculopharyngeal / drug therapy
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Muscular Dystrophy, Oculopharyngeal / genetics
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Muscular Dystrophy, Oculopharyngeal / metabolism
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Mutation
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Poly(A)-Binding Protein II / genetics
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Poly(A)-Binding Protein II / metabolism
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
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Superoxide Dismutase-1
Substances
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Agrin
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Anti-Bacterial Agents
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Apoptosis Regulatory Proteins
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Laminin
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Poly(A)-Binding Protein II
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SOD1 protein, human
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laminin alpha 2
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Sod1 protein, mouse
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Superoxide Dismutase
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Superoxide Dismutase-1
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Minocycline
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Doxycycline