Cited by 113Parkinson's Disease Mechanisms and TreatmentsHistone Deacetylase Inhibitors ResearchNuclear Receptors and Signaling

Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition

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Kidd, Sarah K., Schneider, Jay S.·2010·Brain Research

Abstract

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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  1. Przedborski S Jackson-Lewis V 1998 Mechanisms of MPTP toxicity Mov Disord 13 1 35 8 9613716
  2. Speciale SG 2002 MPTP: insights into parkinsonian neurodegeneration Neurotoxicol Teratol 24 607 20 12200192

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Authors
Kidd, S. K., & Schneider, J. S.
Affiliations
Thomas Jefferson University (US)
Corresponding author
Schneider, Jay S.
Venue
Brain Research
Publisher
Elsevier BV
Published
2010-10
Volume
1354
Pages
172-178
ISSN
0006-8993 (ISSN-L)
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
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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