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Elife. 2015 Dec 17;4. pii: e10891. doi: 10.7554/eLife.10891.

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

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
2
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
3
Department of Neurology, University of Texas Medical Branch, Galveston, United States.
4
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
5
Institute for Translational Neuroscience, University of Minnesota, Minnesota, United States.
6
Department of Neuroscience, Baylor College of Medicine, Houston, 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.

KEYWORDS:

ataxin-1; biochemistry; immunotherapy; mouse; oligomers; propagation

PMID:
26673892
PMCID:
PMC4821792
DOI:
10.7554/eLife.10891
[Indexed for MEDLINE]
Free PMC Article

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