Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease.

Abstract

Ceruloplasmin is an iron-export ferroxidase that is abundant in plasma and also expressed in glia. We found a ∼80% loss of ceruloplasmin ferroxidase activity in the substantia nigra of idiopathic Parkinson disease (PD) cases, which could contribute to the pro-oxidant iron accumulation that characterizes the pathology. Consistent with a role for ceruloplasmin in PD etiopathogenesis, ceruloplasmin knockout mice developed parkinsonism that was rescued by iron chelation. Additionally, peripheral infusion of ceruloplasmin attenuated neurodegeneration and nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model for PD. These findings show, in principle, that intravenous ceruloplasmin may have therapeutic potential in PD.

• Authors: Scott Ayton, Peng Lei, James A Duce, Bruce X W Wong, Amelia Sedjahtera, Paul A Adlard, Ashley I Bush, David I Finkelstein
• Journal: Annals of neurology (Ann Neurol) Vol. 73 Issue 4 Pg. 554-9 (Apr 2013) ISSN: 1531-8249 [Electronic] United States
• PMID: 23424051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Neurological Association.

Chemical References

• Dopamine Agents
• Iron Chelating Agents
• Pyridones
• Deferiprone
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Ceruloplasmin

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Aged
• Animals
• Case-Control Studies
• Ceruloplasmin (deficiency, metabolism, therapeutic use)
• Deferiprone
• Disease Models, Animal
• Dopamine Agents
• Female
• Humans
• Iron Chelating Agents (therapeutic use)
• Male
• Mice
• Mice, Knockout
• Parkinson Disease (drug therapy, etiology, metabolism, pathology)
• Pyridones (therapeutic use)
• Substantia Nigra (metabolism)