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.

journal_name

J Clin Biochem Nutr

authors

Teraoka M,Nakaso K,Kusumoto C,Katano S,Tajima N,Yamashita A,Zushi T,Ito S,Matsura T

doi

10.3164/jcbn.D-11-00030

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

122-7

issue

2

eissn

0912-0009

issn

1880-5086

pii

jcbnD-11-00030

journal_volume

51

pub_type

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