Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes

  1. Cristian A Lasagna-Reeves
  2. Maxime WC Rousseaux
  3. Marcos J Guerrero-Munoz
  4. Luis Vilanova-Velez
  5. Jeehye Park
  6. Lauren See
  7. Paymaan Jafar-Nejad
  8. Ronald Richman
  9. Harry T Orr
  10. Rakez Kayed
  11. Huda Y Zoghbi  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. University of Texas Medical Branch, United States
  3. University of Minnesota, United States

Abstract

Previously we reported that ATXN1 oligomers are the primary drivers of toxicity in Spinocerebellar ataxia type 1 (SCA1; Lasagna-Reeves et al., 2015). Here we report that polyQ ATXN1 oligomers can propagate locally in vivo in mice predisposed to SCA1 following intracerebral oligomeric tissue inoculation. Our data also show that targeting these oligomers with passive immunotherapy leads to some improvement in motor coordination in SCA1 mice and to a modest increase in their life span. These findings provide evidence that oligomer propagation is regionally limited in SCA1 and that immunotherapy targeting extracellular oligomers can mildly modify disease phenotypes.

Article and author information

Author details

  1. Cristian A Lasagna-Reeves

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  2. Maxime WC Rousseaux

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  3. Marcos J Guerrero-Munoz

    Department of Neurology, University of Texas Medical Branch, Galveston, United States
    Competing interests
    No competing interests declared.
  4. Luis Vilanova-Velez

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  5. Jeehye Park

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  6. Lauren See

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  7. Paymaan Jafar-Nejad

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  8. Ronald Richman

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  9. Harry T Orr

    Institute for Translational Neuroscience, University of Minnesota, Minnesota, United States
    Competing interests
    No competing interests declared.
  10. Rakez Kayed

    Department of Neurology, University of Texas Medical Branch, Galveston, United States
    Competing interests
    No competing interests declared.
  11. Huda Y Zoghbi

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    For correspondence
    hzoghbi@bcm.edu
    Competing interests
    Huda Y Zoghbi, Senior editor, eLife.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#AN-1013) of Baylor College of Medicine

Copyright

© 2015, Lasagna-Reeves et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Cristian A Lasagna-Reeves
  2. Maxime WC Rousseaux
  3. Marcos J Guerrero-Munoz
  4. Luis Vilanova-Velez
  5. Jeehye Park
  6. Lauren See
  7. Paymaan Jafar-Nejad
  8. Ronald Richman
  9. Harry T Orr
  10. Rakez Kayed
  11. Huda Y Zoghbi
(2015)
Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes
eLife 4:e10891.
https://doi.org/10.7554/eLife.10891

Share this article

https://doi.org/10.7554/eLife.10891

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