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Sensitization of Neuronal Cells to Oxidative Stress with Mutated Human α‐Synuclein
Author(s) -
Ko Liwen,
Mehta Nitin D.,
Farrer Matthew,
Easson Colin,
Hussey Jennifer,
Yen Samuel,
Hardy John,
Yen ShuHui C.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752546.x
Subject(s) - oxidative stress , transfection , mutant , alpha synuclein , reactive oxygen species , pathogenesis , microbiology and biotechnology , biology , chemistry , parkinson's disease , biochemistry , gene , immunology , medicine , disease
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.