Biomol Ther.
2013 May;21(3):222-228.
Valproic Acid Regulates alpha-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes
- Affiliations
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- 1Department of Neuroscience, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea. kjjasmine@hanmail.net
- 2Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
- 3Department of Pharmacology, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
- 4Center for Neuroscience Research, SMART Institute Advanced Biomedical Sciences, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
- 5Department of Psychiatry, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Abstract
- 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.
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