Applicant for Position of Director, Eccles Institute of Neuroscience.Professor Ashley Bush, Head, Oxidation Biology Laboratory, Mental Health Research Institute.
Iron accumulates abnormally in affected neurons in Alzheimer’s disease (AD) and Parkinson’s disease (PD), and can contribute to disease pathogenesis. We recently reported a major role for β-amyloid precursor protein (APP) in the regulation of iron homeostasis through its ferroxidase activity (Duce et al, Cell 142, 857-867 (2010)). The inhibition of this activity by zinc (transferring from amyloid) contributes to the elevation of neuronal iron, and may lie upstream of features of the disorder such as oxidative damage. Following this, we have recently reported that tau plays an essential role in this neuronal iron export mechanism, by facilitating APP maturation and trafficking to the neuronal surface where it interacts with ferroportin (Lei et al, Nature Medicine, 2012 online). We found that tau KO mice develop age-dependent neurodegeneration with cognitive loss and parkinsonism, which was rescued by the gentle iron complexing agent, clioquinol. The link between APP and tau in this iron-related export pathway is important because not only does tau accumulate in characteristic tangle pathology, but also tau is a risk gene in common for AD and PD, and mutations of tau cause frontotemporal dementia with parkinsonism (FTDP-17). Targeting the iron accumulation may be therapeutically useful.
Professor Ashley Bush (MB BS, DPM, FRANZCP, PhD, FTSE) heads the Oxidation Biology Laboratory at the Mental Health Research Institute, The University of Melbourne, is Biomarker co-director within the Australian Imaging Biomarker Lifestyle Study (AIBL), Chief Scientific Officer of the CRC for Mental Health, lecturer in psychiatry at Harvard Medical School and adjunct professor of neuroscience at Cornell University. He has received numerous awards including the Australia Fellowship from the NHMRC. Professor Bush has authored over 240 publications, with >16,000 citations, 21 patents and founded 3 biotechnology companies. He discovered the interaction of beta-amyloid with zinc as a major factor in Alzheimer’s disease