OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Alpha-synuclein regulates neuronal levels of manganese and calcium.

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Dučić, T.* ; Carboni, E.* ; Lai, B.* ; Chen, S.* ; Michalke, B. ; Lázaro, D.F.* ; Outeiro, T.F.* ; Bähr, M.* ; Barski, E.* ; Lingor, P.*

Alpha-synuclein regulates neuronal levels of manganese and calcium.

ACS Chem. Neurosci. 6, 1769-1779 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords X-ray Fluorescence ; Xanes Spectroscopy ; Alpha-synuclein ; Calcium ; Manganese
e-ISSN 1948-7193
Journal ACS Chemical Neuroscience
Quellenangaben Volume: 6, Issue: 10, Pages: 1769-1779 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit BioGeoChemistry and Analytics (BGC)