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The Journal of Neuroscience, August 1, 2002, 22(15):6578-6586
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, and
Samuel
David
Centre for Research in Neuroscience, The Montreal General Hospital
Research Institute and McGill University, Montreal, Quebec, Canada, H3G
1A4
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.
Key words:
iron; neurodegeneration; free radicals; lipid
peroxidation; ferroxidase; aceruloplasminemia; Parkinson's disease; oxidative stress
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156578-09$05.00/0
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