Abstract
We sought genetic evidence for the involvement of neuronal vascular endothelial growth factor (VEGF) in amyotrophic lateral sclerosis (ALS). Mice expressing human ALS mutant superoxide dismutase-1 (SOD1) were crossed with mice that overexpress VEGF in neurons (VEGF+/+). We report that SOD1(G93A)/VEGF+/+ double-transgenic mice show delayed motor neuron loss, delayed motor impairment, and prolonged survival compared with SOD1(G93A) single transgenics. These findings indicate that neuronal VEGF protects against motor neuron degeneration, and may have therapeutic implications for ALS.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Amyotrophic Lateral Sclerosis / metabolism*
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Amyotrophic Lateral Sclerosis / mortality
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Amyotrophic Lateral Sclerosis / pathology
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Animals
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Disease Models, Animal
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Gene Expression Regulation / physiology*
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Gene Expression Regulation, Enzymologic / physiology
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Motor Neurons / pathology
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Nerve Degeneration / enzymology
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Nerve Degeneration / metabolism*
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Nerve Degeneration / pathology
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Nerve Degeneration / prevention & control*
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Superoxide Dismutase / biosynthesis
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Superoxide Dismutase / genetics
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Superoxide Dismutase-1
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Survival Rate
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Vascular Endothelial Growth Factor A / biosynthesis*
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Vascular Endothelial Growth Factor A / genetics*
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Vascular Endothelial Growth Factor A / physiology
Substances
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SOD1 protein, human
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Vascular Endothelial Growth Factor A
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Sod1 protein, mouse
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Superoxide Dismutase
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Superoxide Dismutase-1