Florey Department of Neuroscience and Mental Health - Theses
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ItemThe role of extracellular ferritin in ferroptosis: Implications for neurodegenerative disease( 2019)Abnormal iron elevation and the associated cell death pathway ferroptosis are implicated in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Ferritin, the major iron binding protein of the body, is present in cerebrospinal fluid (CSF) where it has been shown to be associated with Alzheimer’s disease progression, however the function of extracellular ferritin is not known. Ferroptosis involves the degradation of cytosolic ferritin, but whether extracellular ferritin impacts on ferroptosis is unknown. To better understand the role of extracellular ferritin in neurodegenerative diseases, this project aims 1) to characterize extracellular ferritin in response to iron and 2) to investigate the effect of extracellular ferritin on neuronal ferroptotic cell death in vitro. This thesis demonstrated that the expressions of intracellular and extracellular ferritin are associated with intracellular iron levels in both glia and neuronal cell lines. Extracellular vesicles from cell culture and from brain tissue were found to contain ferritin. Though the levels of soluble ferritin secreted by neurons increased with an increase in intracellular iron levels, the levels of vesicular ferritin remained unchanged. The levels of iron in neuronal extracellular vesicles increased with cellular iron burden. Endocytosis of soluble apo-H ferritin protected cultured neurons against ferroptosis. Taken together, changes in biofluid ferritin levels may represent a response to ferroptosis in neurodegenerative diseases.