Abstract
Amyotrophic Lateral Sclerosis (ALS), which accounts for the majority of motor neuron disorders, is a progressive and fatal neurodegenerative disease leading to complete paralysis of skeletal muscles and premature death usually by respiratory failure. About 10% of all ALS cases are inherited, with the responsible genes having been identified in approximately 30% of these individuals. Mutations in the copper-zinc superoxide dismutase (SOD1) gene were the first to be recognized nearly twenty years ago, and since then different animal models, in particular transgenic rodents, have been developed. They replicate many of the clinical, neuropathological and molecular features of ALS patients and have contributed significantly to our understanding of the pathogenic mechanisms of this disease. Although results obtained so far with mutant SOD1 mice have not translated into effective therapies in ALS patients, these models still represent the only experimentally accessible system to study multiple aspects of disease pathogenesis and to provide proof-of-principle for the development of new therapeutic strategies. This review will examine the most recent discoveries obtained from these animal models in an attempt to elucidate the complex mechanisms of the disease. In particular it will focus on the contribution of multiple cell types in governing the disease development and progression.
Keywords: Amyotrophic lateral sclerosis, motor neuron, transgenic mouse models, SOD1
CNS & Neurological Disorders - Drug Targets
Title: Unraveling the Complexity of Amyotrophic Lateral Sclerosis: Recent Advances from the Transgenic Mutant SOD1 Mice
Volume: 9 Issue: 4
Author(s): M. Peviani, I. Caron, C. Pizzasegola, F. Gensano, M. Tortarolo and C. Bendotti
Affiliation:
Keywords: Amyotrophic lateral sclerosis, motor neuron, transgenic mouse models, SOD1
Abstract: Amyotrophic Lateral Sclerosis (ALS), which accounts for the majority of motor neuron disorders, is a progressive and fatal neurodegenerative disease leading to complete paralysis of skeletal muscles and premature death usually by respiratory failure. About 10% of all ALS cases are inherited, with the responsible genes having been identified in approximately 30% of these individuals. Mutations in the copper-zinc superoxide dismutase (SOD1) gene were the first to be recognized nearly twenty years ago, and since then different animal models, in particular transgenic rodents, have been developed. They replicate many of the clinical, neuropathological and molecular features of ALS patients and have contributed significantly to our understanding of the pathogenic mechanisms of this disease. Although results obtained so far with mutant SOD1 mice have not translated into effective therapies in ALS patients, these models still represent the only experimentally accessible system to study multiple aspects of disease pathogenesis and to provide proof-of-principle for the development of new therapeutic strategies. This review will examine the most recent discoveries obtained from these animal models in an attempt to elucidate the complex mechanisms of the disease. In particular it will focus on the contribution of multiple cell types in governing the disease development and progression.
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Cite this article as:
Peviani M., Caron I., Pizzasegola C., Gensano F., Tortarolo M. and Bendotti C., Unraveling the Complexity of Amyotrophic Lateral Sclerosis: Recent Advances from the Transgenic Mutant SOD1 Mice, CNS & Neurological Disorders - Drug Targets 2010; 9 (4) . https://dx.doi.org/10.2174/187152710791556096
DOI https://dx.doi.org/10.2174/187152710791556096 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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