Garringer, Holly J.Irimia, Jose M.Li, WeiGoodwin, Charles B.Richine, BrianaActon, AnthonyChan, Rebecca J.Peacock, MunroMuhoberac, Barry B.Ghetti, BernardinoVidal, Ruben2017-05-222017-05-222016-08-30Garringer, H. J., Irimia, J. M., Li, W., Goodwin, C. B., Richine, B., Acton, A., … Vidal, R. (2016). Effect of Systemic Iron Overload and a Chelation Therapy in a Mouse Model of the Neurodegenerative Disease Hereditary Ferritinopathy. PLoS ONE, 11(8), e0161341. http://doi.org/10.1371/journal.pone.0161341https://hdl.handle.net/1805/12670Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuroferritinopathy or hereditary ferritinopathy (HF). HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic iron-containing ferritin inclusion bodies (IBs) in glia and neurons throughout the central nervous system (CNS) and in tissues of multiple organ systems. Herein, using primary mouse embryonic fibroblasts from a mouse model of HF, we show significant intracellular accumulation of ferritin and an increase in susceptibility to oxidative damage when cells are exposed to iron. Treatment of the cells with the iron chelator deferiprone (DFP) led to a significant improvement in cell viability and a decrease in iron content. In vivo, iron overload and DFP treatment of the mouse model had remarkable effects on systemic iron homeostasis and ferritin deposition, without significantly affecting CNS pathology. Our study highlights the role of iron in modulating ferritin aggregation in vivo in the disease HF. It also puts emphasis on the potential usefulness of a therapy based on chelators that can target the CNS to remove and redistribute iron and to resolubilize or prevent ferritin aggregation while maintaining normal systemic iron stores.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesFerritin light chainGene mutationsNeuroferritinopathyHereditary ferritinopathyIronArticle