alpha-synuclein is a cellular ferrireductaseα-突触核蛋白是一个细胞ferrireductase.pdfVIP

Alpha-Synuclein Is a Cellular Ferrireductase Paul Davies, Dima Moualla, David R. Brown* Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom Abstract a-synuclein (aS) 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 aS 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 aS is a cellular ferrireductase, responsible for reducing iron (III) to bio available iron (II). The recombinant form of the protein has a VMax of 2.72 nmols/min/mg and Km 23 mM. This activity is also evident in lysates from neuronal cell lines overexpressing aS. This activity is dependent on copper bound to aS as a cofactor and NADH as an electron donor. Overexpression of a-synuclein by cells significantly increases the percentage of iron (II) in cells. The common disease mutations associated with increased susceptibility to PD show differences in activity or iron (II) levels. This discovery may well provide new therapeutic targets for PD and Lewy body dementias. Citation: Davies P, Moualla D, Brown DR (2011) Alpha-Synuclein Is a Cellular Ferrireductase. PLoS ONE 6(1): e15814. doi:10.1371/journal.pone.0015814 Editor: Mark P. Mattson, National Institute on Aging Intramural Research Program, United States of America Received November 5, 2010; Accepted December 2, 2010; Published January 10, 2011 Copyright: 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. Funding