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

First Author  Patel BN Year  2002
Journal  J Neurosci Volume  22
Issue  15 Pages  6578-86
PubMed ID  12151537 Mgi Jnum  J:78092
Mgi Id  MGI:2183328 Doi  10.1523/JNEUROSCI.22-15-06578.2002
Citation  Patel BN, et al. (2002) Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. J Neurosci 22(15):6578-86
abstractText  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.
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