Premium
α‐Synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson's disease
Author(s) -
Hasegawa Takafumi,
Matsuzaki-Kobayashi Michiko,
Takeda Atsushi,
Sugeno Naoto,
Kikuchi Akio,
Furukawa Katsutoshi,
Perry George,
Smith Mark A.,
Itoyama Yasuto
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.03.018
Subject(s) - neurodegeneration , parkinson's disease , chemistry , mitochondrion , programmed cell death , oxidative stress , biochemistry , pathogenesis , tyrosinase , microbiology and biotechnology , apoptosis , oxidative phosphorylation , biology , disease , enzyme , medicine , pathology , immunology
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.