Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury

Bharatkumar N. Patel, Robert J. Dunn, Suh Young Jeong, Qinzhang Zhu, Jean Pierre Julien, Samuel David

Research output: Contribution to journalArticlepeer-review

273 Scopus citations

Abstract

Ceruloplasmin is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form. We have previously reported that a glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed in the mammalian CNS. To better understand the role of ceruloplasmin in iron homeostasis in the CNS, we generated a ceruloplasmin gene-deficient (Cp-/-) mouse. Adult Cp-/- mice showed increased iron deposition in several regions of the CNS such as the cerebellum and brainstem. Increased lipid peroxidation was also seen in some CNS regions. Cerebellar cells from neonatal Cp-/- mice were also more susceptible to oxidative stress in vitro. Cp-/- mice showed deficits in motor coordination that were associated with a loss of brainstem dopaminergic neurons. These results indicate that ceruloplasmin plays an important role in maintaining iron homeostasis in the CNS and in protecting the CNS from iron-mediated free radical injury. Therefore, the antioxidant effects of ceruloplasmin could have important implications for various neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease in which iron deposition is known to occur.

Original languageEnglish (US)
Pages (from-to)6578-6586
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number15
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

Keywords

  • Aceruloplasminemia
  • Ferroxidase
  • Free radicals
  • Iron
  • Lipid peroxidation
  • Neurodegeneration
  • Oxidative stress
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

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