The anticonvulsant properties of VPA (valproic acid), a branched short-chain fatty acid, were serendipitously discovered in 1963. Since then, therapeutic roles of VPA have increased to include bipolar disorder and migraine prophylaxis, and have more recently been proposed in cancer, Alzheimer's disease and HIV treatment. These numerous therapeutic roles elevate VPA to near ‘panacea’ level. Surprisingly, the mechanisms of action of VPA in the treatment of many of these disorders remain unclear, although it has been shown to alter a wide variety of signalling pathways and a small number of direct targets. To analyse the mechanism of action of VPA, a number of studies have defined the structural characteristics of VPA-related compounds giving rise to distinct therapeutic and cellular effects, including adverse effects such as teratogenicity and hepatotoxicity. These studies raise the possibility of identifying target-specific novel compounds, providing better therapeutic action or reduced side effects. This short review will describe potential therapeutic pathways targeted by VPA, and highlight studies showing structural constraints necessary for these effects.
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October 2009
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Conference Article|
September 21 2009
Structure–function studies for the panacea, valproic acid
Nicole Terbach;
Nicole Terbach
1Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, U.K.
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Robin S.B. Williams
Robin S.B. Williams
1
1Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, U.K.
1To whom correspondence should be addressed (email Robin.Williams@rhul.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 02 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (5): 1126–1132.
Article history
Received:
July 02 2009
Citation
Nicole Terbach, Robin S.B. Williams; Structure–function studies for the panacea, valproic acid. Biochem Soc Trans 1 October 2009; 37 (5): 1126–1132. doi: https://doi.org/10.1042/BST0371126
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