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Background

Intraneuronal iron imbalance is a predominant catalyst for reactive oxygen species production, particularly within iron accumulating neurodegenerative diseases such as Alzheimer's disease (AD). In AD, amyloid precursor protein (APP) has historically been associated with amyloid-β (Aβ) derived neurotoxicity, but we recently discovered that APP also has a role in neuronal iron homeostasis by, in part, promoting iron efflux through cell surface stabilization of the iron pore ferroportin.

Methods

The processing of APP was modified in cultured cells by secretase inhibition (TAPI or bIV) or depletion (ADAM10 or BACE1 siRNAi) in the presence (addition to media) or absence (chelation by deferiprone) of iron. Alternatively, iron homeostasis in N2A transfected with familiar APP mutations was also investigated. Cell surface biotinylation and fluorescence-activated cell sorting were used to examine changes in …