Cited by 379Neurological diseases and metabolismIron Metabolism and DisordersTrace Elements in Health

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Ceruloplasmin Regulates Iron Levels in the CNS and Prevents Free Radical Injury

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Patel, Bharatkumar N., Dunn, Robert J., Jeong, Suh Young, Zhu, Qinzhang, Julien, Jean-Pierre, David, Samuel·2002·The Journal of Neuroscience

DOI 10.1523/jneurosci.22-15-06578.2002PMC PMC6758125

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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.

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Authors: Patel, B. N., Dunn, R. J., Jeong, S. Y., Zhu, Q., Julien, J.-P., & David, S.
Affiliations: Montreal General Hospital (CA)
ORCID: Jeong, Suh Young
Julien, Jean-Pierre
David, Samuel
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2002-08-01
Volume: 22
Issue: 15
Pages: 6578-6586
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.22-15-06578.2002
PMC: PMC6758125
OpenAlex: W1595395957
Cited by: 379
References: 51
Citations by year: 2026: 5 · 2025: 12 · 2024: 10 · 2023: 12 · 2022: 16 · 2021: 14 · 2020: 12 · 2019: 11 · 2018: 22 · 2017: 17 · 2016: 11 · 2015: 24 · 2014: 24 · 2013: 15 · 2012: 22
FWCI: 10.71
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Parkinson's Disease Foundation
Canadian Institutes of Health Research
Topics: Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: ceruloplasmin, iron homeostasis, central nervous system, ferroxidase, oxidative damage, oxidative stress, lipid peroxidation, cerebellum, brainstem, dopaminergic neurons, motor coordination deficits, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, iron accumulation
MeSH terms: Animals, Astrocytes, Brain Stem, Cell Survival, Cells, Cultured, Central Nervous System, Ceruloplasmin, Disease Models, Animal, Free Radicals, Iron, Liver, Neurons, Transferrin, Lipid Peroxidation, Mice, Knockout, Oxidative Stress, Gene Targeting, Motor Skills Disorders, Mice

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Ceruloplasmin Regulates Iron Levels in the CNS and Prevents Free Radical Injury

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