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Cited by 25Alzheimer's disease research and treatmentsHistone Deacetylase Inhibitors ResearchCholesterol and Lipid Metabolism

Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion

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Dresselhaus, Erica, Duerr, James M., Vincent, Fabien, Sylvain, Emily K., Beyna, Mercedes, Lanyon, Lorraine F., LaChapelle, Erik, Pettersson, Martin +2 more·2018·PLOS ONE
DOI 10.1371/journal.pone.0194661PMC PMC5868809
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Abstract

Despite the important role of apolipoprotein E (apoE) secretion from astrocytes in brain lipid metabolism and the strong association of apoE4, one of the human apoE isoforms, with sporadic and late onset forms of Alzheimer's disease (AD) little is known about the regulation of astrocytic apoE. Utilizing annotated chemical libraries and a phenotypic screening strategy that measured apoE secretion from a human astrocytoma cell line, inhibition of pan class I histone deacetylases (HDACs) was identified as a mechanism to increase apoE secretion. Knocking down select HDAC family members alone or in combination revealed that inhibition of the class I HDAC family was responsible for enhancing apoE secretion. Knocking down LXRα and LXRβ genes revealed that the increase in astrocytic apoE in response to HDAC inhibition occurred via an LXR-independent pathway. Collectively, these data suggest that pan class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion.

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Authors
Dresselhaus, E., Duerr, J. M., Vincent, F., Sylvain, E. K., Beyna, M., Lanyon, L. F., LaChapelle, E., Pettersson, M., Bales, K. R., & Ramaswamy, G.
Affiliations
Pfizer (United States) (US)
Corresponding author
  • Bales, Kelly R.
  • Ramaswamy, Gayathri
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-03-26
Volume
13
Issue
3
Pages
e0194661
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0194661
PMC
PMC5868809
OpenAlex
W2794406984
Cited by
25
References
11
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 8 · 2019: 4 · 2018: 2
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
Pfizer
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
astrocytes, class I histone deacetylases, histone deacetylase inhibition, APOE ε4, Alzheimer's disease, liver X receptor, brain lipid metabolism, astrocytoma cells
MeSH terms
Liver X Receptors, Benzenesulfonamides, Apolipoproteins E, Astrocytes, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Fluorocarbons, Genotype, Histone Deacetylases, Humans, Hydrocarbons, Fluorinated, Protein Binding, RNA, Messenger, Sulfonamides, Protein Isoforms, RNA Interference, RNA, Small Interfering, Small Molecule Libraries, Histone Deacetylase Inhibitors, ATP Binding Cassette Transporter 1

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