α-Synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson's disease

Takafumi Hasegawa, Michiko Matsuzaki-Kobayashi, Atsushi Takeda, Naoto Sugeno, Akio Kikuchi, Katsutoshi Furukawa, George Perry, Mark A. Smith, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2147-2152
Number of pages6
JournalFEBS Letters
Volume580
Issue number8
DOIs
Publication statusPublished - 2006 Apr 3

Keywords

  • Dopamine
  • Mitochondria
  • Neurodegeneration
  • Parkinson's disease
  • Quinone
  • α-Synuclein

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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