Abstract:
:Parkinson's disease is a major neurodegenerative disease involving the selective degeneration of dopaminergic neurons and α-synuclein containing Lewy bodies formation in the substantia nigra. Although α-synuclein is a key molecule for both dopaminergic neuron death and the formation of inclusion bodies, the mechanism of α-synuclein induction of Parkinson's disease-related pathogenesis is not understood. In the present study, we found that the interaction between dopamine and α-synuclein requires the oxidation of dopamine. Furthermore, we examined the protective effect of chlorogenic acid, a major polyphenol contained in coffee, against α-syn and dopamine-related toxicity. Chlorogenic acid inhibits several DA/α-synuclein-related phenomenon, including the oxidation of dopamine, the interaction of oxidized dopamine with α-synuclein, and the oligomerization of α-synuclein under dopamine existing conditions in vitro. Finally, we showed that the cytoprotective effect against α-synuclein-related toxicity in PC12 cells that can be controlled by the Tet-Off system. Although the induction of α-synuclein in catecholaminergic PC12 cells causes a decrease in cell viability, chlorogenic acid rescued this cytotoxicity significantly in a dose dependent manner. These results suggest that the interaction of oxidized DA with α-synuclein may be a novel therapeutic target for Parkinson's disease, and polyphenols, including chlorogenic acid, are candidates as protective and preventive agents for Parkinson's disease onset.
journal_name
J Clin Biochem Nutrjournal_title
Journal of clinical biochemistry and nutritionauthors
Teraoka M,Nakaso K,Kusumoto C,Katano S,Tajima N,Yamashita A,Zushi T,Ito S,Matsura Tdoi
10.3164/jcbn.D-11-00030subject
Has Abstractpub_date
2012-09-01 00:00:00pages
122-7issue
2eissn
0912-0009issn
1880-5086pii
jcbnD-11-00030journal_volume
51pub_type
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