A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells
Joint Authors
Pollock, Tanner B.
Mack, Jacob M.
Day, Ryan J.
Isho, Noail F.
Brown, Raquel J.
Oxford, Alexandra E.
Morrison, Brad E.
Hayden, Eric J.
Rohn, Troy T.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-06
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Despite the fact that harboring the apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer’s disease (AD), the exact mechanism by which apoE4 contributes to disease progression remains unknown.
Recently, we demonstrated that a 151 amino-terminal fragment of apoE4 (nApoE41-151) localizes within the nucleus of microglia in the human AD brain, suggesting a potential role in gene expression.
In the present study, we investigated this possibility utilizing BV2 microglia cells treated exogenously with nApoE41-151.
The results indicated that nApoE41-151 leads to morphological activation of microglia cells through, at least in part, the downregulation of a novel ER-associated protein, CXorf56.
Moreover, treatment of BV2 cells with nApoE41-151 resulted in a 68-fold increase in the expression of the inflammatory cytokine, TNFα, a key trigger of microglia activation.
In this regard, we also observed a specific binding interaction of nApoE41-151 with the TNFα promoter region.
Collectively, these data identify a novel gene-regulatory pathway involving CXorf56 that may link apoE4 to microglia activation and inflammation associated with AD.
American Psychological Association (APA)
Pollock, Tanner B.& Mack, Jacob M.& Day, Ryan J.& Isho, Noail F.& Brown, Raquel J.& Oxford, Alexandra E.…[et al.]. 2019. A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1203957
Modern Language Association (MLA)
Pollock, Tanner B.…[et al.]. A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1203957
American Medical Association (AMA)
Pollock, Tanner B.& Mack, Jacob M.& Day, Ryan J.& Isho, Noail F.& Brown, Raquel J.& Oxford, Alexandra E.…[et al.]. A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1203957
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203957