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Deferiprone Rescues Behavioral Deficits Induced by Mild Iron Exposure in a Mouse Model of Alpha-Synuclein Aggregation

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD...

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Detalles Bibliográficos
Autores principales: Carboni, Eleonora, Tatenhorst, Lars, Tönges, Lars, Barski, Elisabeth, Dambeck, Vivian, Bähr, Mathias, Lingor, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570801/
https://www.ncbi.nlm.nih.gov/pubmed/28623611
http://dx.doi.org/10.1007/s12017-017-8447-9
Descripción
Sumario:Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic mouse model. Beginning from day 100, mice were treated with deferiprone (DFP), a ferric chelator that is able to cross the blood–brain barrier and is currently used in clinics as treatment for hemosiderosis. Our paradigm resulted in an impairment of the learning abilities in the rotarod task and the novel object recognition test. DFP treatment significantly improved the performance in both tasks. Although this was not accompanied by alterations in aSyn aggregation, our results support DFP as possible therapeutic option in PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12017-017-8447-9) contains supplementary material, which is available to authorized users.