Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1

被引：79

作者：

Cvetanovic, Marija ^{[1
]}

Patel, Jay M. ^{[1
]}

Marti, Hugo H. ^{[2
]}

Kini, Ameet R. ^{[3
,4
]}

Opal, Puneet ^{[1
,5
]}

机构：

[1] Northwestern Univ, Davee Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA

[2] Univ Heidelberg, Inst Physiol & Pathophysiol, Heidelberg, Germany

[3] Loyola Univ Chicago, Stritch Sch Med, Dept Pathol, Maywood, IL USA

[4] Loyola Univ Chicago, Stritch Sch Med, Cardinal Bernardin Canc Ctr, Maywood, IL USA

[5] Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, Chicago, IL 60611 USA

来源：

NATURE MEDICINE | 2011年 / 17卷 / 11期

基金：

美国国家卫生研究院;

关键词：

MOTOR-NEURON DEGENERATION; HYPOXIA-RESPONSE ELEMENT; TRANSGENIC MICE; TRINUCLEOTIDE REPEAT; SCA1; NEURODEGENERATION; VEGF; PROTEIN; EXPRESSION; DISORDERS;

D O I：

10.1038/nm.2494

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1445 / 1447

页数：3

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