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

Nature Medicine volume 17, pages 14451447 (2011) | Download Citation


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.

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We thank H. Zoghbi (Baylor College of Medicine) and H. Orr (University of Minnesota) for generously providing ATXN1 constructs and the SCA1 mouse models, and S. Leibovich (University of Medicine and Dentistry of New Jersey) and P. D'Amore (Harvard Medical School) for VEGF luciferase reporter constructs. We also thank K. Gobeske for assistance with the intracerebroventricular delivery methods, A. Ma for help with pathological analyses and V. Brandt for editorial assistance. This work was funded by US National Institutes of Health grants K02 NS051340, R21 NS060080 and R01 NS062051 (P.O.); a US National Organization for Rare Disorders grant (P.O.), a US Brain Research Foundation Grant (P.O.) and a US National Ataxia Foundation grant (P.O.). M.C. received funding from the US National Institutes of Health training grant T32. The authors wish to dedicate this manuscript to fellow scientist T. Spann, who is currently fighting amyotrophic lateral sclerosis.

Author information


  1. Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Marija Cvetanovic
    • , Jay M Patel
    •  & Puneet Opal
  2. Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.

    • Hugo H Marti
  3. Department of Pathology and Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

    • Ameet R Kini
  4. Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Puneet Opal


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P.O., A.R.K. and M.C. conceived of the study and designed the experiments. M.C. and J.M.P. conducted and analyzed the experiments. H.H.M. provided and characterized the VEGF-transgenic mice. P.O., M.C. and A.R.K. wrote the paper, and J.M.P. helped with revising the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Puneet Opal.

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