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




Deferiprone Rescues Behavioral Deficits Induced by Mild Iron Exposure in a Mouse Model of Alpha-Synuclein Aggregation - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

NeuroMolecular Medicine

pp 1–13

First Online: 16 June 2017Received: 04 February 2017Accepted: 06 June 2017DOI: 10.1007-s12017-017-8447-9

Cite this article as: Carboni, E., Tatenhorst, L., Tönges, L. et al. Neuromol Med 2017. doi:10.1007-s12017-017-8447-9

Abstract

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.

KeywordsAlpha-synuclein Iron Deferiprone Parkinson’s disease Rotarod Novel object recognition test Electronic supplementary materialThe online version of this article doi:10.1007-s12017-017-8447-9 contains supplementary material, which is available to authorized users.





Autor: Eleonora Carboni - Lars Tatenhorst - Lars Tönges - Elisabeth Barski - Vivian Dambeck - Mathias Bähr - Paul Lingor

Fuente: https://link.springer.com/







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