title: Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Lasagna-Reeves
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
authors.forename: Maxime Wc
authors.initials: MW
authors.lastname: Rousseaux
authors.affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, United States.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Guerrero-Munoz
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
authors.forename: Luis
authors.initials: L
authors.lastname: Vilanova-Velez
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
authors.forename: Jeehye
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: See
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
authors.forename: Paymaan
authors.initials: P
authors.lastname: Jafar-Nejad
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Richman
authors.affiliation: Institute for Translational Neuroscience, University of Minnesota, Minnesota, United States.
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
authors.affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, United States.
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.|Department of Neuroscience, Baylor College of Medicine, Houston, United states.
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D000067696:Ataxin-1 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D007116:Immunization, Passive; D051379:Mice; D020754:Spinocerebellar Ataxias / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000067696:Ataxin-1
keywords: ataxin-1; biochemistry; immunotherapy; mouse; oligomers; propagation