Sensitization of Neuronal Cells to Oxidative Stress with Mutated Human α‐Synuclein
Open Access
- 1 December 2000
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 75 (6) , 2546-2554
- https://doi.org/10.1046/j.1471-4159.2000.0752546.x
Abstract
Linkage of α‐synuclein (α‐SN) mutations tofamilial Parkinson's disease (PD) and presence of α‐SN as a majorconstituent of Lawy body in both sporadic and familial PD implicate α‐SNabnormality in PD pathogenesis. Here we demonstrate that overexpression ofwild‐type or mutant α‐SN does not cause any deleterious effect on thegrowth or continued propagation of transfected human cells, but overproductionof mutant α‐SN heightens their sensitivity to menadione‐inducedoxidative injury. Such enhanced vulnerability is more pronounced in neuronaltransfectants than in their nonneuronal counterparts and is associated withincreased production of reactive oxygen species. The data suggest that mutatedα‐SN, especially with an alanine‐to‐proline substitution at residue 30,sensitizes neuronal cells to oxidative damage.Keywords
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