title: Cytoprotective effect of chlorogenic acid against α-synuclein-related toxicity in catecholaminergic PC12 cells.
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.
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, 86, Nishi-cho, Yonago 683-8503, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Teraoka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaso
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kusumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katano
authors.forename: Naoko
authors.initials: N
authors.lastname: Tajima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.forename: Teppei
authors.initials: T
authors.lastname: Zushi
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Matsura