Unraveling the mechanisms involved in motor neuron degeneration in ALS

Although Charcot described amyotrophic lateral sclerosis (ALS) more than 130 years ago, the mechanism underlying the characteristic selective degeneration and death of motor neurons in this common adult motor neuron disease has remained a mystery. There is no effective remedy for this progressive, f...

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Bibliographic Details
Published in:Annual review of neuroscience 2004-01, Vol.27 (1), p.723-749
Main Authors: BRUIJN, Lucie I, MILLER, Timothy M, CLEVELAND, Don W
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - etiology
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - metabolism
Animals
Biological and medical sciences
Cells
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dyneins - metabolism
Genetics
Glutamic Acid - metabolism
Glutamic Acid - toxicity
Humans
Medical sciences
Models, Neurological
Motor ability
Motor Neurons - metabolism
Motor Neurons - pathology
Mutation
Nerve Degeneration - etiology
Nerve Degeneration - genetics
Nerve Degeneration - metabolism
Neurofilament Proteins - metabolism
Neurology
Neurons
Superoxide Dismutase - deficiency
Superoxide Dismutase - genetics
Therapy
Vascular Endothelial Growth Factor A - metabolism
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Summary:Although Charcot described amyotrophic lateral sclerosis (ALS) more than 130 years ago, the mechanism underlying the characteristic selective degeneration and death of motor neurons in this common adult motor neuron disease has remained a mystery. There is no effective remedy for this progressive, fatal disorder. Modern genetics has now identified mutations in one gene [Cu/Zn superoxide dismutase (SOD1)] as a primary cause and implicated others [encoding neurofilaments, cytoplasmic dynein and its processivity factor dynactin, and vascular endothelial growth factor (VEGF)] as contributors to, or causes of, motor neuron diseases. These insights have enabled development of model systems to test hypotheses of disease mechanism and potential therapies. Along with errors in the handling of synaptic glutamate and the potential excitotoxic response this provokes, these model systems highlight the involvement of nonneuronal cells in disease progression and provide new therapeutic strategies.
ISSN:0147-006X
1545-4126
DOI:10.1146/annurev.neuro.27.070203.144244