Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition
Open accessAbstract
Although the pathophysiological processes involved in dopamine (DA) neuron degeneration in Parkinson's disease (PD) are not completely known, apoptotic cell death has been suggested to be involved and can be modeled in DAergic cell lines using the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP(+)). Recently, it has been suggested that histone deacetylase inhibitors (HDACIs) may reduce apoptotic cell death in various model systems. However, their utility in interfering with DA cell death remains unclear. The HDACIs sodium butyrate (NaB), valproate (VPA) and suberoylanilide hydroxamic acid (SAHA) were tested for their ability to prevent MPP(+)-mediated cytotoxicity in human derived SK-N-SH and rat derived MES 23.5 cells. All three HDACIs at least partially prevented MPP(+)-mediated apoptotic cell death. The protective effects of these HDACIs coincided with significant increases in histone acetylation. These results suggest that HDACIs may be potentially neuroprotective against DA cell death and should be explored further in animal models of PD.
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“Additionally, SCFAs are involved in neurotransmitter production [75] and neuroprotection and can penetrate the blood–brain barrier [76]; therefore, they have been proposed as potential novel antidepressants [77].”
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- Authors
- Kidd, S. K., & Schneider, J. S.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Schneider, Jay S.
- ORCID
- Schneider, Jay S.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 1354
- Pages
- 172-178
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2941155
- OpenAlex
- W2064753279
- Cited by
- 113
- References
- 32
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 14 · 2022: 8 · 2021: 6 · 2020: 17 · 2019: 8 · 2018: 2 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 3 · 2013: 7 · 2012: 5
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- F.M. Kirby Foundation
- NIEHS (T32 ES07282)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- histone deacetylase inhibitors, MPP+, dopaminergic neurons, Parkinson's disease, neuroprotection, apoptosis, histone acetylation, sodium butyrate, valproic acid, vorinostat, SK-N-SH cells
- MeSH terms
- Vorinostat, Acetylation, Analysis of Variance, Animals, Cell Line, Cells, Cultured, Dopamine, Histones, Humans, Hydroxamic Acids, Immunohistochemistry, Nerve Degeneration, Neurons, Valproic Acid, 1-Methyl-4-phenylpyridinium, Apoptosis, Butyric Acid, Rats, Histone Deacetylase Inhibitors
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