Abstract
Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, dominantly inherited neurodegenerative disease caused by expansion of a glutamine repeat tract in ataxin-1 (ATXN1). Although the precise function of ATXN1 remains elusive, it seems to be involved in transcriptional repression. We find that mutant ATXN1 represses transcription of the neurotrophic and angiogenic factor vascular endothelial growth factor (VEGF). Genetic overexpression or pharmacologic infusion of recombinant VEGF mitigates SCA1 pathogenesis, suggesting a new therapeutic strategy for this disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ataxin-1
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Ataxins
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Disease Models, Animal
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Humans
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Mice
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Mice, Transgenic
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Spinocerebellar Ataxias / drug therapy*
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Spinocerebellar Ataxias / pathology
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Spinocerebellar Ataxias / physiopathology*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism*
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Vascular Endothelial Growth Factor A / therapeutic use*
Substances
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ATXN1 protein, human
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Ataxin-1
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Ataxins
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Atxn1 protein, mouse
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Nerve Tissue Proteins
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Nuclear Proteins
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Vascular Endothelial Growth Factor A