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

Cristian A. Lasagna-Reeves, Maxime W.C. Rousseaux, Marcos J. Guerrero-Munoz, Luis Vilanova-Velez, Jeehye Park, Lauren See, Paymaan Jafar-Nejad, Ronald Richman, Harry T. Orr, Rakez Kayed, Huda Y. Zoghbi

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Article numbere10891
JournaleLife
Volume4
Issue numberDECEMBER2015
DOIs
StatePublished - Dec 17 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Lasagna-Reeves, C. A., Rousseaux, M. W. C., Guerrero-Munoz, M. J., Vilanova-Velez, L., Park, J., See, L., Jafar-Nejad, P., Richman, R., Orr, H. T., Kayed, R., & Zoghbi, H. Y. (2015). Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows spinocerebellar ataxia type 1 phenotypes. eLife, 4(DECEMBER2015), [e10891]. https://doi.org/10.7554/eLife.10891