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Biomol Ther (Seoul). 2013 May 30;21(3):222-8. doi: 10.4062/biomolther.2013.006.

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

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Departments of Neuroscience, School of Medicine, Konkuk University, Seoul 143-701 ; Center for Neuroscience Research, SMART Institute Advanced Biomedical Sciences, School of Medicine, Konkuk University, Seoul 143-701.


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.


Acetylation; JNK; Neuroprotection; Stability; Valproic acid; α-synuclein

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