Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

Liangliang Zhao, Majda Hadziahmetovic, Chenguang Wang, Xueying Xu, Ying Song, H. A. Jinnah, Jolanta Wodzinska, Jared Iacovelli, Natalie Wolkow, Predrag Krajacic, Alyssa Cwanger Weissberger, John Connelly, Michael Spino, Michael K. Lee, James Connor, Benoit Giasson, Z. Leah Harris, Joshua L. Dunaief

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons.

Original languageEnglish (US)
Pages (from-to)958-974
Number of pages17
JournalJournal of Neurochemistry
Issue number5
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
This work was funded by The Paul and Evanina Bell Mackall Foundation Trust, The F.M. Kirby Foundation, National Institutes of Health, (Grant/Award Number: ''NIH EY015240''). The Dunaief lab receives research funding from ApoPharma, Inc., and JLD is co-inventor on a patent pending for use of deferiprone for age-related macular degeneration. Michael Spino, John Connelly, and Jolanta Wodzinska are employees of ApoPharma. All experiments were conducted in compliance with the ARRIVE guidelines.

Publisher Copyright:
© 2015 International Society for Neurochemistry.


  • ceruloplasmin/Hephaestin
  • deferiprone
  • glia
  • iron
  • neurodegeneration
  • oxidative stress


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