title: 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: Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors: Scott
authors: S
authors: Ayton
authors: Peng
authors: P
authors: Lei
authors: James A
authors: JA
authors: Duce
authors: Bruce X W
authors: BX
authors: Wong
authors: Amelia
authors: A
authors: Sedjahtera
authors: Paul A
authors: PA
authors: Adlard
authors: Ashley I
authors: AI
authors: Bush
authors: David I
authors: DI
authors: Finkelstein
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use; D000077543:Deferiprone; D004195:Disease Models, Animal; D015259:Dopamine Agents; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011728:Pyridones / Q000627:therapeutic use; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002570:Ceruloplasmin