The role of apoptosis in neuromuscular diseases and prospects for anti-apoptosis therapy.

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.

• Authors: Jeffrey B Miller, Mahasweta Girgenrath
• Journal: Trends in molecular medicine (Trends Mol Med) Vol. 12 Issue 6 Pg. 279-86 (Jun 2006) ISSN: 1471-4914 [Print] England
• PMID: 16650805 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Agrin
• Anti-Bacterial Agents
• Apoptosis Regulatory Proteins
• Laminin
• Poly(A)-Binding Protein II
• SOD1 protein, human
• laminin alpha 2
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1
• Minocycline
• Doxycycline

Topics

• Agrin (genetics, metabolism)
• Amyotrophic Lateral Sclerosis (drug therapy, enzymology, genetics)
• Animals
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Apoptosis (genetics)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Clinical Trials as Topic
• Disease Models, Animal
• Doxycycline (pharmacology, therapeutic use)
• Gene Expression Regulation (drug effects)
• Genetic Therapy (methods)
• Humans
• Laminin (genetics, metabolism)
• Mice
• Minocycline (pharmacology, therapeutic use)
• Muscular Dystrophies (genetics, metabolism, therapy)
• Muscular Dystrophy, Oculopharyngeal (drug therapy, genetics, metabolism)
• Mutation
• Poly(A)-Binding Protein II (genetics, metabolism)
• Superoxide Dismutase (genetics, metabolism)
• Superoxide Dismutase-1