title: Ceruloplasmin and β-amyloid precursor protein confer neuroprotection in traumatic brain injury and lower neuronal iron.
abstract: Traumatic brain injury (TBI) is in part complicated by pro-oxidant iron elevation independent of brain hemorrhage. Ceruloplasmin (CP) and β-amyloid protein precursor (APP) are known neuroprotective proteins that reduce oxidative damage through iron regulation. We surveyed iron, CP, and APP in brain tissue from control and TBI-affected patients who were stratified according to time of death following injury. We observed CP and APP induction after TBI accompanying iron accumulation. Elevated APP and CP expression was also observed in a mouse model of focal cortical contusion injury concomitant with iron elevation. To determine if changes in APP or CP were neuroprotective we employed the same TBI model on APP(-/-) and CP(-/-) mice and found that both exhibited exaggerated infarct volume and iron accumulation postinjury. Evidence supports a regulatory role of both proteins in defence against iron-induced oxidative damage after TBI, which presents as a tractable therapeutic target.
authors: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health.
authors: Scott
authors: S
authors: Ayton
authors: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Moses
authors: M
authors: Zhang
authors: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health.
authors: Blaine R
authors: BR
authors: Roberts
authors: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health.
authors: Linh Q
authors: LQ
authors: Lam
authors: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health.
authors: Monica
authors: M
authors: Lind
authors: Department of Pathology, and The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Catriona
authors: C
authors: McLean
authors: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health; Department of Pathology, and The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Ashley I
authors: AI
authors: Bush
authors: Department of Anatomy and Cell Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Tony
authors: T
authors: Frugier
authors: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Peter J
authors: PJ
authors: Crack
authors: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, North Yorkshire, UK. Electronic address: james.duce@florey.edu.au.
authors: James A
authors: JA
authors: Duce
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000473:pathology; D002570:Ceruloplasmin / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000293:injuries / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D007501:Iron; D002570:Ceruloplasmin
keywords: Amyloid precursor protein; Ceruloplasmin; Free radicals; Iron; Mouse models; Traumatic brain injury