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Iron, Ferroptosis and Neurodegenerative Disease

EVENT: 
Seminar
Who Should Attend: 
Researchers

Abstract 

Recent research has implicated increased brain iron as a trait that can propel various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Motor Neuron disease and the complications of stroke. Ageing itself causes iron to increase in the brain to a point where it is “too much of a good thing” and can set up conditions that lead to neurodegeneration. During childhood and reproductive life, iron recruitment is geared towards avoiding iron deficiency, but there is no natural mechanism for off-loading excess iron. After reproductive life the systems that harvest iron so efficiently do not turn off, and lead to accumulation in tissues that are not normally shed, like brain. In the C. elegans model of ageing, we find that such iron elevation limits lifespan. In Alzheimer's disease brain iron elevation is associated with the rate of cognitive loss, lipid peroxidation products and features of the regulated cell death mechanism, ferroptosis. Anti-ferroptosis agents have been effective in animal models of neurodegenerative disease, and a recent phase 2 clinical trial of the anti-ferroptotic chelator deferiprone in Parkinson’s disease lowered nigral iron and improved clinical readouts. We are currently testing this drug in a phase 2 RCT in Alzheimer’s disease. CuATSM, has recently reported benefits in phase 1 studies of Parkinson’s disease and Motor Neuron Disease, and we have identified that it possesses potent anti-ferroptotic properties.

Dr. Bush's Figure

Publications

Brent R Stockwell, José Pedro Friedmann Angeli, Hülya Bayir, Ashley I Bush, Marcus Conrad, Scott J Dixon, Simone Fulda, Sergio Gascón, Stavroula K Hatzios, Valerian E Kagan, Kay Noel, Xuejun Jiang, Andreas Linkermann, Maureen E Murphy, Michael Overholtzer, Atsushi Oyagi, Gabriela C Pagnussat, Jason Park, Qitao Ran, Craig S Rosenfeld, Konstantin Salnikow, Daolin Tang, Frank M Torti, Suzy V Torti, Shinya Toyokuni, K A Woerpel, Donna D Zhang
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Cell, 171 (2), 273-285 2017 Oct 5
Scott Ayton, Yamin Wang, Ibrahima Diouf, Julie A Schneider, John Brockman, Martha Clare Morris, Ashley I Bush
Brain Iron Is Associated With Accelerated Cognitive Decline in People With Alzheimer Pathology
Mol Psychiatry 2019 Feb 18 [Online ahead of print]
Adam Southon, Kathryn Szostak, Karla M Acevedo, Krista A Dent, Irene Volitakis, Abdel A Belaidi, Kevin J Barnham, Peter J Crouch, Scott Ayton, Paul S Donnelly, Ashley I Bush
Cu II (Atsm) Inhibits Ferroptosis: Implications for Treatment of Neurodegenerative Disease
Br J Pharmacol, 177 (3), 656-667 Feb 2020

When

Thursday, March 5, 2020 - 10:00am

Where

785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Kelsey Library

More Information

Darlene H. White