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- Title
α-Synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson’s disease
- Authors
Hasegawa, Takafumi; Matsuzaki-Kobayashi, Michiko; Takeda, Atsushi; Sugeno, Naoto; Kikuchi, Akio; Furukawa, Katsutoshi; Perry, George; Smith, Mark A.; Itoyama, Yasuto
- Abstract
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.
- Subjects
CATECHOL; METABOLISM; PARKINSON'S disease; TETRACYCLINE
- Publication
FEBS Letters, 2006, Vol 580, Issue 8, p2147
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2006.03.018