The DOI matches its OpenAlex record; 13 of the 13 references it cites were found in a registry or an index.
Biochemical, Molecular and Epigenetic Mechanisms of Valproic Acid Neuroprotection
Abstract
Valproic acid (VPA, 2-propylpentanoic acid) has been widely used as an antiepileptic drug and for the therapy of bipolar disorders for several years. Its mechanism of action was initially found to be primarily related to neurotransmission and modulation of intracellular pathways. More recently, it emerged as an anti-neoplastic agent as well, by acting on cell growth, differentiation and apoptosis. Here, it mainly exerts its effect by regulating gene expression at the molecular level, through epigenetic mechanisms. In particular, it has been demonstrated the effect of VPA in chromatin remodeling, as VPA directly inhibits histone deacetylases (HDACs) activity. Interestingly, it has been observed that these biochemical and molecular pathways are involved not only in beneficial effect of VPA against epilepsy and malignancies, but they are also responsible for more general neuroprotective mechanisms. In particular, it has been demonstrated that VPA is neuroprotective in several models of neurodegenerative diseases. Moreover, due to the involvement of the VPA-affected mechanisms in complex behaviors, VPA is increasingly used as a psychotherapeutic agent. This review summarizes the more recent data on VPA neuroprotective mechanisms at the biochemical, molecular and epigenetic levels, focusing on both in vitro and in vivo models of neurodegenerative diseases. In particular, attention is paid to mechanisms by which VPA affects neuronal survival/apoptosis and proliferation/differentiation balance, as well as synaptic plasticity, by acting both directly on neurons and indirectly through glial cells. Perspective applications of the VPA neuroprotective potential in human neurodegenerative diseases are discussed, when relevant.
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Cites
Function and regulation of CREB family transcription factors in the nervous system
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The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
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“VPA, in addition to selectively inhibiting the catalytic activity of class I HDACs, induces proteasomal degradation of HDAC2, in contrast to other HDAC inhibitors such as trichostatin A (TSA) [175].”
ResultBrichta, L. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg256 · Cited by 382
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Valproate Induces Replication-independent Active DNA Demethylation
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Protein kinase C overactivity impairs prefrontal cortical regulation of working memory
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“The VPA induced apoptosis of microglia cells is mainly due to the HDACs inhibition, as demonstrated by the fact that also TSA and sodium butyrate (SB), two structurally dissimilar HDACs inhibitors, induce microglial apoptosis [213].”
Background
Cited by
Mechanisms of epileptogenesis and potential treatment targets
Pitkänen, A., & Lukasiuk, K. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70310-0 · Cited by 614
Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline
Cho, K.-O., Lybrand, Z. R., Ito, N., Brulet, R., Tafacory, F., Zhang, L., Good, L., Ure, K., Kernie, S. G., Birnbaum, S. G., et al. (2015) · Nature Communications · doi:10.1038/ncomms7606 · Cited by 451
Targeting the correct HDAC(s) to treat cognitive disorders
Fischer, A., Sananbenesi, F., Mungenast, A., & Tsai, L.-H. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.003 · Cited by 354
Valproate reopens critical-period learning of absolute pitch
Gervain, J., Vines, B. W., Chen, L. M., Seo, R. J., Hensch, T. K., Werker, J. F., & Young, A. H. (2013) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2013.00102 · Cited by 151
Millan, M. J., Goodwin, G. M., Meyer-Lindenberg, A., & Ove Ögren, S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.01.016 · Cited by 132
Metadata
- Authors
- Monti, B., Polazzi, E., & Contestabile, A.
- Venue
- Current Molecular Pharmacology
- Publisher
- Bentham Science Publishers
- Published
- 2009-01-01
- Volume
- 2
- Issue
- 1
- Pages
- 95-109
- ISSN
- 1874-4672 (ISSN-L)
- OpenAlex
- W2098145833
- Cited by
- 239
- References
- 13
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- closed
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- Monti, B., Polazzi, E., & Contestabile, A. (2009). Biochemical, Molecular and Epigenetic Mechanisms of Valproic Acid Neuroprotection. Current Molecular Pharmacology. https://doi.org/10.2174/1874-470210902010095
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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