Abstract
The process of neuronal degeneration in motor neurone disease is complex. Several genetic alterations may be involved in motor neurone injury in familial amyotrophic lateral sclerosis, less is known about the genetic and environmental factors involved in the commoner sporadic form of the disease. Most is known about the mechanisms of motor neurone degeneration in the subtype of disease caused by SOD1 mutations, but even here there appears to be a complex interplay between multiple pathogenic processes including oxidative stress, protein aggregation, mitochondrial dysfunction excitotoxicity, and impaired axonal transport. There is new evidence that non-neuronal cells in the vicinity of motor neurones may contribute to neuronal injury. The final demise of motor neurones is likely to involve a programmed cell death pathway resembling apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amyotrophic Lateral Sclerosis / epidemiology
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / pathology
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Axonal Transport / genetics
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Biological Transport
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Calcium-Binding Proteins / genetics
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Cell Aggregation
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Cell Death / physiology
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Chromosomes, Human, Pair 9 / genetics
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DNA Helicases
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Dynactin Complex
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Environment
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Exons / genetics
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Humans
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Kv Channel-Interacting Proteins
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Microtubule-Associated Proteins / genetics
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Mitochondrial Myopathies / epidemiology
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Mitochondrial Myopathies / pathology
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Mitochondrial Myopathies / physiopathology
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Motor Neuron Disease / epidemiology
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Motor Neuron Disease / genetics*
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Motor Neuron Disease / pathology*
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Multifunctional Enzymes
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Nerve Degeneration / epidemiology
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Nerve Degeneration / pathology*
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Neural Pathways / pathology*
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Oxidative Stress / physiology
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Point Mutation / genetics
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RNA Helicases / genetics
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Risk Factors
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Superoxide Dismutase / genetics
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Superoxide Dismutase-1
Substances
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Calcium-Binding Proteins
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Dynactin Complex
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KCNIP1 protein, human
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Kv Channel-Interacting Proteins
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Microtubule-Associated Proteins
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Multifunctional Enzymes
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SOD1 protein, human
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Superoxide Dismutase
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Superoxide Dismutase-1
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SETX protein, human
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DNA Helicases
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RNA Helicases