Sensitization of Neuronal Cells to Oxidative Stress with Mutated Human α‐Synuclein

: 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...

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Published in:Journal of neurochemistry 2000-12, Vol.75 (6), p.2546-2554
Main Authors: Ko, Li‐wen, Mehta, Nitin D., Farrer, Matthew, Easson, Colin, Hussey, Jennifer, Yen, Samuel, Hardy, John, Yen, Shu‐Hui C.
Format: Article
Language:English
Subjects:
a-Synuclein
alpha-Synuclein
Biological and medical sciences
Cell Line
Cell Survival - drug effects
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dose-Response Relationship, Drug
Humans
Immunoblotting
Kidney - cytology
Kidney - drug effects
Kidney - metabolism
Medical sciences
Menadione
Mutation
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - pharmacology
Neurology
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Oxidative stress
Oxidative Stress - drug effects
Oxidative Stress - genetics
Parkinson Disease - genetics
Parkinson's disease
Reactive Oxygen Species - metabolism
RNA, Messenger - metabolism
Sulfhydryl Compounds - metabolism
Synucleins
Tetrazolium Salts
Thiazoles
Transfection
Vitamin K - pharmacology
α‐Synuclein
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Summary:: 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.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.2000.0752546.x