Valproic Acid Regulates α-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes

丙戊酸通过 JNK 通路调节大鼠原代星形胶质细胞中的 α-突触核蛋白表达

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作者:Jung Nam Kim, Min Kyeong Kim, Kyu Suk Cho, Chang Soon Choi, Seung Hwa Park, Sung-Il Yang, So Hyun Joo, Jin Hee Park, Geonho Bahn, Chan Young Shin, He-Jin Lee, Seol-Heui Han, Kyoung Ja Kwon

Abstract

Although the role of α-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of α-synuclein are unclear yet. We recently reported that α-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing α-synuclein in neuron, on α-synuclein expression in rat primary astrocytes. VPA concentrationdependently increased the protein expression level of α-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted α-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in α-synuclein. Whether the increased α-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.

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