α‐Synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson's disease
Open Access
- 15 March 2006
- journal article
- Published by Wiley in FEBS Letters
- Vol. 580 (8), 2147-2152
- https://doi.org/10.1016/j.febslet.2006.03.018
Abstract
Free radicals, including dopamine (DA)‐oxidized metabolites, have long been implicated in pathogenesis of Parkinson's disease (PD). However, the relationships between such oxidative stresses and α‐synuclein (α‐S), a major constituent of Lewy bodies, remain unknown. In this study, we established neuronal cells that constitutively express α‐S and tetracycline‐regulated tyrosinase. While tyrosinase overexpression induced apoptosis, co‐expression of wild type or A53T mutant human α‐S with tyrosinase further exacerbated cell death. In this process, the formation of α‐S oligomers and the reduction in mitochondrial membrane potential were demonstrated. This cellular model may reconstitute the pathological metabolism of α‐S in the synucleinopathy and provide a useful tool to explore possible pathomechanisms of nigral degeneration in PD.This publication has 32 references indexed in Scilit:
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