Biometals in Neurodegenerative Diseases: Mechanisms and Therapeutics

Associate Professor Anthony White is a Group Leader at the QIMR Berghofer Medical Research Institute in Queensland, Australia. He is also an Honorary Principal Research Fellow at The University of Melbourne, and an Adjunct Professor in Translational Neuroscience at A.I. Virtanen Institute, University of Eastern Finland. He investigates the cellular pathology of neurodegenerative diseases, and has a strong focus on the role of biometals in neurodegenerative processes, and as novel targets for neurotherapeutics. His research has led to the development of first-in-class metal-drugs as a potential new therapeutic approach to treat motor neuron, Parkinson’s and Alzheimer’s diseases through the targeting of complementary biometal pathways in these disorders. He has published over 120 original research papers, reviews and book chapters, is Associate Editor for Neurochemistry International and co-founded a start-up biotech company (Procypra Therapeutics) that has delivered a novel copper-based metal-drug to clinical trials for motor neuron disease. He has been awarded prestigious research fellowships including National Health and Medical Research Council (NHMRC) R.D Wright Fellowship, and Senior Research Fellowship, and Australian Research Council (ARC) Future Fellowship. His research has contributed to the understanding of copper interactions with the amyloid precursor protein (APP) and amyloid beta peptide in Alzheimer’s disease, and more recently, the key role of copper in cell signaling and neuroinflammatory processes.

Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. He served on numerous toxicology panels (Institute of Medicine, US Environmental Protection Agency, Center for Disease Control), and is a member of the Neurotoxicology and Alcohol study section (NIH). Research in our lab focuses on the following topics: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress. Our studies are designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences.

Dr. Lucio G. Costa is Professor of Toxicology at the University of Washington in Seattle, and of Pharmacology/Toxicology at the University of Parma Medical School. He received a doctorate in Pharmacology from the University of Milano in 1977, and was a postdoctoral fellow at the University of Texas at Houston. He is a member of several national and international professional organizations, a Fellow of the Academy of Toxicological Sciences, and a European Certified Toxicologist. He received various award for his scientific accomplishments, including the Achievement Award from the Society of Toxicology. He serves in various editorial capacities for several toxicology journals, and is an active manuscript and grant reviewer. Dr. Costa has been the member of dozens of panels and committees at the national and international level dealing with toxicology and risk assessment issues. He has chaired and/or organized symposia at scientific meetings in the United States and internationally. He has been teaching classes in the area of toxicology, neurotoxicology and pharmacology to graduate and medical students for 30 years. He keeps an active research program in the area of neurotoxicology.

Dr. Bush is a Professor at the Florey Institute of Neuroscience and Mental Health in Parkville, Victoria, Australia. He is also the Director of the Oxidation Biology Unit. Dr. Bush’s laboratory looks at how key proteins interact inappropriately with metals in the brain to cause oxidative stress in diseases including Alzheimer’s and Parkinson’s. He is actively working to develop disease-modifying drugs for Alzheimer’s and Parkinson's diseases, as well as blood tests for the disorders.