Parkinson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Parkinson's Disease, including details on symptoms, treatment, genetics, medication.

Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: implications for selective neurodegeneration in Parkinson's disease.

Hasegawa T, Matsuzaki-Kobayashi M, Takeda A, Sugeno N, Kikuchi A, Furukawa K, Perry G, Smith MA, Itoyama Y

Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi 980-8574, Japan.

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 alpha-synuclein (alpha-S), a major constituent of Lewy bodies, remain unknown. In this study, we established neuronal cells that constitutively express alpha-S and tetracycline-regulated tyrosinase. While tyrosinase overexpression induced apoptosis, co-expression of wild type or A53T mutant human alpha-S with tyrosinase further exacerbated cell death. In this process, the formation of alpha-S oligomers and the reduction in mitochondrial membrane potential were demonstrated. This cellular model may reconstitute the pathological metabolism of alpha-S in the synucleinopathy and provide a useful tool to explore possible pathomechanisms of nigral degeneration in PD.

Published 28 March 2006 in FEBS Lett, 580(8): 2147-52.
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