Davies, P., Moualla, D. and Brown, D. R., 2011. α-Synuclein is a cellular ferrireductase. PLoS ONE, 6 (1), e15814.
alpha-synuclein (alpha S) is a cellular protein mostly known for the association of its aggregated forms with a variety of diseases that include Parkinson's disease and Dementia with Lewy Bodies. While the role of alpha S in disease is well documented there is currently no agreement on the physiological function of the normal isoform of the protein. Here we provide strong evidence that alpha S is a cellular ferrireductase, responsible for reducing iron (III) to bio available iron (II). The recombinant form of the protein has a V-Max of 2.72 nmols/min/mg and K-m 23 mu M. This activity is also evident in lysates from neuronal cell lines overexpressing alpha S. This activity is dependent on copper bound to alpha S as a cofactor and NADH as an electron donor. Overexpression of alpha-synuclein by cells significantly increases the percentage of iron (II) in cells. The common disease mutations associated with increased susceptibility to PD show no differences in activity or iron (II) levels. This discovery may well provide new therapeutic targets for PD and Lewy body dementias.
|Item Type ||Articles|
|Creators||Davies, P., Moualla, D. and Brown, D. R.|
|Departments||Faculty of Science > Biology & Biochemistry|
|Publisher Statement||Brown_PlosOne_2011_6_1.pdf: © 2011 Davies et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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