TY - JOUR
T1 - α-Synuclein facilitates the toxicity of oxidized catechol metabolites
T2 - Implications for selective neurodegeneration in Parkinson's disease
AU - Hasegawa, Takafumi
AU - Matsuzaki-Kobayashi, Michiko
AU - Takeda, Atsushi
AU - Sugeno, Naoto
AU - Kikuchi, Akio
AU - Furukawa, Katsutoshi
AU - Perry, George
AU - Smith, Mark A.
AU - Itoyama, Yasuto
N1 - Funding Information:
This work was supported by Grants-in-Aid for scientific research from the ministry of Education, Culture, Sports, Science and Technology of Japan and by the Kanae Foundation for Life & Socio-Medical Science.
PY - 2006/4/3
Y1 - 2006/4/3
N2 - 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.
AB - 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.
KW - Dopamine
KW - Mitochondria
KW - Neurodegeneration
KW - Parkinson's disease
KW - Quinone
KW - α-Synuclein
UR - http://www.scopus.com/inward/record.url?scp=33645244513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645244513&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2006.03.018
DO - 10.1016/j.febslet.2006.03.018
M3 - Article
C2 - 16567160
AN - SCOPUS:33645244513
VL - 580
SP - 2147
EP - 2152
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 8
ER -
