Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion.
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....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5868809?pdf=render |
| _version_ | 1828260416938049536 |
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| author | Erica Dresselhaus James M Duerr Fabien Vincent Emily K Sylvain Mercedes Beyna Lorraine F Lanyon Erik LaChapelle Martin Pettersson Kelly R Bales Gayathri Ramaswamy |
| author_facet | Erica Dresselhaus James M Duerr Fabien Vincent Emily K Sylvain Mercedes Beyna Lorraine F Lanyon Erik LaChapelle Martin Pettersson Kelly R Bales Gayathri Ramaswamy |
| author_sort | Erica Dresselhaus |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T03:22:33Z |
| format | Article |
| id | doaj.art-214aaa2673324b92bf01f2321f37451d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T03:22:33Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-214aaa2673324b92bf01f2321f37451d2022-12-22T03:04:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019466110.1371/journal.pone.0194661Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion.Erica DresselhausJames M DuerrFabien VincentEmily K SylvainMercedes BeynaLorraine F LanyonErik LaChapelleMartin PetterssonKelly R BalesGayathri RamaswamyDespite 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.http://europepmc.org/articles/PMC5868809?pdf=render |
| spellingShingle | Erica Dresselhaus James M Duerr Fabien Vincent Emily K Sylvain Mercedes Beyna Lorraine F Lanyon Erik LaChapelle Martin Pettersson Kelly R Bales Gayathri Ramaswamy Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion. PLoS ONE |
| title | Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion. |
| title_full | Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion. |
| title_fullStr | Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion. |
| title_full_unstemmed | Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion. |
| title_short | Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion. |
| title_sort | class i hdac inhibition is a novel pathway for regulating astrocytic apoe secretion |
| url | http://europepmc.org/articles/PMC5868809?pdf=render |
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