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Open Access Green as soon as Postprint is submitted to ZB.
Alpha-synuclein regulates neuronal levels of manganese and calcium.
ACS Chem. Neurosci. 6, 1769-1779 (2015)
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
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
Publisher
American Chemical Society (ACS)
Reviewing status
Peer reviewed
Institute(s)
Research Unit BioGeoChemistry and Analytics (BGC)