Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes
CA Lasagna-Reeves, MWC Rousseaux… - Elife, 2015 - elifesciences.org
Elife, 2015•elifesciences.org
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 …
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 …
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.
DOI: http://dx.doi.org/10.7554/eLife.10891.001
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