Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury.
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.
Patel
Bharatkumar N
BN
Centre for Research in Neuroscience, The Montreal General Hospital Research Institute and McGill University, Montreal, Quebec, Canada, H3G 1A4.
Dunn
Robert J
RJ
Jeong
Suh Young
SY
Zhu
Qinzhang
Q
Julien
Jean-Pierre
JP
David
Samuel
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism*; D018390:Gene Targeting; D007501:Iron / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019957:Motor Skills Disorders / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
D005609:Free Radicals; D014168:Transferrin; D007501:Iron; D002570:Ceruloplasmin