Effect of systemic iron overload and a chelation therapy in a mouse model of the neurodegenerative disease hereditary ferritinopathy

Holly Garringer, Jose M. Irimia, Wei Li, Charles B. Goodwin, Briana Richine, Anthony Acton, Rebecca Chan, Munro Peacock, Barry B. Muhoberac, Bernardino Ghetti, Ruben Vidal

Research output: Contribution to journalArticle

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Abstract

Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuro-ferritinopathy 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.

Original languageEnglish (US)
Article numbere0161341
JournalPLoS One
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2016

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Neurodegenerative diseases
Chelation Therapy
iron overload
Iron Overload
chelation
neurodegenerative diseases
Chelation
Neurodegenerative Diseases
ferritin
Iron
animal models
iron
Ferritins
therapeutics
Neurology
central nervous system
Central Nervous System
Chelating Agents
chelating agents
movement disorders

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Effect of systemic iron overload and a chelation therapy in a mouse model of the neurodegenerative disease hereditary ferritinopathy. / Garringer, Holly; Irimia, Jose M.; Li, Wei; Goodwin, Charles B.; Richine, Briana; Acton, Anthony; Chan, Rebecca; Peacock, Munro; Muhoberac, Barry B.; Ghetti, Bernardino; Vidal, Ruben.

In: PLoS One, Vol. 11, No. 8, e0161341, 01.08.2016.

Research output: Contribution to journalArticle

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AU - Acton, Anthony

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