Alpha-synuclein ferrireductase activity is detectible in vivo, is altered in Parkinson's disease and increases the neurotoxicity of DOPAL

McDowall, Jennifer S.; Ntai, Ioanna; Honeychurch, Kevin C; Hart, John P; Colin, Philippe; Schneider, Bernard L.; Brown, David R.

Abstract

© 2017 Elsevier Inc. The normal cellular role of α-synuclein is of potential importance in understanding diseases in which an aggregated form of the protein has been implicated. A potential loss or change in the normal function of α-synuclein could play a role in the aetiology of diseases such as Parkinson's disease. Recently, it has been suggested that α-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Experiments were carried out to determine if such activity could be measured in vivo. Experiments with rats overexpressing human α-synuclein in nigral dopaminergic neurons demonstrated a correlation between α-synuclein expression and ferrireductase activity. Furthermore, studies on tissue from Parkinson's disease patient brains showed a significant decrease in ferrireductase activity, possibly due to deposition of large amounts of inactive protein. Cellular studies suggest that increase ferrireductase activity results in increased levels of dopamine metabolites and increased sensitivity to the toxicity of DOPAL. These findings demonstrate that α-synuclein ferrireductase activity is present in vivo and its alteration may play a role in neuron loss in disease.

Citation

McDowall, J. S., Ntai, I., Honeychurch, K. C., Hart, J. P., Colin, P., Schneider, B. L., & Brown, D. R. (2017). Alpha-synuclein ferrireductase activity is detectible in vivo, is altered in Parkinson's disease and increases the neurotoxicity of DOPAL. Molecular and Cellular Neuroscience, 85, 1-11. https://doi.org/10.1016/j.mcn.2017.08.001

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2017
• Online Publication Date: Aug 12, 2017
• Publication Date: Dec 1, 2017
• Deposit Date: Aug 30, 2017
• Publicly Available Date: Aug 12, 2018
• Journal: Molecular and Cellular Neuroscience
• Print ISSN: 1044-7431
• Electronic ISSN: 1095-9327
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 85
• Pages: 1-11
• DOI: https://doi.org/10.1016/j.mcn.2017.08.001
• Keywords: synuclein, iron ferrireductase, DOPAL, neurotoxicity
• Public URL: https://uwe-repository.worktribe.com/output/876870
• Publisher URL: http://dx.doi.org/10.1016/j.mcn.2017.08.001