Browse by author
Lookup NU author(s): Professor Tiago OuteiroORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2015 American Chemical Society. Manganese (Mn) may foster aggregation of alpha-synuclein (αSyn) contributing to the pathogenesis of PD. Here, we examined the influence of αSyn overexpression on distribution and oxidation states of Mn in frozen-hydrated primary midbrain neurons (PMNs) by synchrotron-based X-ray fluorescence (XRF) and X-ray absorption near edge structure spectroscopy (XANES). Overexpression of αSyn increased intracellular Mn levels, whereas levels of Ca, Zn, K, P, and S were significantly decreased. Mn oxidation states were not altered. A strong correlation between Cu-/Mn-levels as well as Fe-/Mn-levels was observed in αSyn-overexpressing cells. Subcellular resolution revealed a punctate or filament-like perinuclear and neuritic distribution of Mn, which resembled the expression of DMT1 and MnSOD. While overexpression of αSyn did not significantly alter the expression patterns of the most-expressed Mn transport proteins (DMT1, VGCC, Fpn1), it attenuated the Mn release from Mn-treated neurons. Thus, these data suggest that αSyn may act as an intracellular Mn store. In total, neurotoxicity in PD could be mediated via regulation of transition metal levels and the metal-binding capacity of αSyn, which could represent a promising therapeutic target for this neurodegenerative disorder.
Author(s): Ducic T, Carboni E, Lai B, Chen S, Michalke B, Lazaro DF, Outeiro TF, Bahr M, Barski E, Lingor P
Publication type: Article
Publication status: Published
Journal: ACS Chemical Neuroscience
Online publication date: 18/08/2015
Acceptance date: 01/01/1900
ISSN (print): 1948-7193
Publisher: American Chemical Society
PubMed id: 26284970
Altmetrics provided by Altmetric