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

• Published in: Biomolecules & therapeutics 2013-05, Vol.21 (3), p.222-228
• Main Authors: Kim, Jung Nam, Kim, Min Kyeong, Cho, Kyu Suk, Choi, Chang Soon, Park, Seung Hwa, Yang, Sung-Il, Joo, So Hyun, Park, Jin Hee, Bahn, Geonho, Shin, Chan Young, Lee, He-Jin, Han, Seol-Heui, Kwon, Kyoung Ja
• Format: Article
• Language: Korean
• Subjects: Acetylation; JNK; Neuroprotection; Stability; Valproic acid; α-synuclein
• ISSN: 1976-9148; 2005-4483

Although the role of ${\alpha}$-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of ${\alpha}$-synuclein are unclear yet. We recently reported that ${\alpha}$-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 ${\alpha}$-synuclein in neuron, on ${\alpha}$-synuclein expression in rat primary astrocytes. VPA concentration-dependently increased the protein expression level of ${\alpha}$-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted ${\alpha}$-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 ${\alpha}$-synuclein. Whether the increased ${\alpha}$-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.