The role of apoptosis in neuromuscular diseases and prospects for anti-apoptosis therapy.
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.
Miller
Jeffrey B
JB
Neuromuscular Biology and Disease Group, Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA. miller@bbri.org
Girgenrath
Mahasweta
M
D018171:Agrin / Q000235:genetics / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D039141:Muscular Dystrophy, Oculopharyngeal / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D039103:Poly(A)-Binding Protein II / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D018171:Agrin; D000900:Anti-Bacterial Agents; D051017:Apoptosis Regulatory Proteins; D007797:Laminin; D039103:Poly(A)-Binding Protein II; C000606290:SOD1 protein, human; C102645:laminin alpha 2; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D008911:Minocycline; D004318:Doxycycline