Abstract
ALS is a relentless neurodegenerative disease in which motor neurons are the susceptible neuronal population. Their death results in progressive paresis of voluntary and respiratory muscles. The unprecedented rate of discoveries over the last two decades have broadened our knowledge of genetic causes and helped delineate molecular pathways. Here we critically review ALS epidemiology, genetics, pathogenic mechanisms, available animal models, and iPS cell technologies with a focus on their translational therapeutic potential. Despite limited clinical success in treatments to date, the new discoveries detailed here offer new models for uncovering disease mechanisms as well as novel strategies for intervention.
Keywords:
Animal models; C9ORF72; Epidemiology; FUS; Genetics; Molecular mechanisms; SOD1; TDP-43; iPSC.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amyotrophic Lateral Sclerosis / epidemiology
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Amyotrophic Lateral Sclerosis / genetics*
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Amyotrophic Lateral Sclerosis / physiopathology
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Animals
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Autophagy-Related Proteins
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C9orf72 Protein / genetics*
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Cell Cycle Proteins / genetics
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DNA-Binding Proteins / genetics*
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Disease Models, Animal
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Frontotemporal Dementia / epidemiology
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Frontotemporal Dementia / genetics*
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Frontotemporal Dementia / physiopathology
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Genes, Modifier / genetics
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Humans
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Induced Pluripotent Stem Cells
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Motor Neuron Disease / epidemiology
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Motor Neuron Disease / genetics
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Motor Neuron Disease / physiopathology
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RNA-Binding Protein FUS / genetics*
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Superoxide Dismutase-1 / genetics*
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Translational Research, Biomedical
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Ubiquitins / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Autophagy-Related Proteins
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C9orf72 Protein
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Cell Cycle Proteins
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DNA-Binding Proteins
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RNA-Binding Protein FUS
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TARDBP protein, human
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UBQLN2 protein, human
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Ubiquitins
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Superoxide Dismutase-1