Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes
| Autor: | Maxime W.C. Rousseaux, Harry T. Orr, Luis Vilanova-Velez, Rakez Kayed, Ronald Richman, Huda Y. Zoghbi, Lauren See, Paymaan Jafar-Nejad, Jeehye Park, Marcos J. Guerrero-Muñoz, Cristian A. Lasagna-Reeves |
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| Rok vydání: | 2015 |
| Předmět: |
Spinocerebellar Ataxia Type 1
Mouse QH301-705.5 Science medicine.medical_treatment Ataxin 1 Biology Biochemistry General Biochemistry Genetics and Molecular Biology Mice ataxin-1 In vivo propagation medicine Extracellular Animals Spinocerebellar Ataxias Biology (General) oligomers General Immunology and Microbiology General Neuroscience Immunization Passive General Medicine Immunotherapy medicine.disease Phenotype 3. Good health Motor coordination Disease Models Animal Treatment Outcome Immunology Spinocerebellar ataxia Cancer research biology.protein Medicine immunotherapy Research Advance |
| Zdroj: | eLife eLife, Vol 4 (2015) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.10891 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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