Skip to main content
Article
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
  • Tanner B. Pollock, Boise State University
  • Jacob M. Mack, Boise State University
  • Noail F. Isho, Boise State University
  • Raquel J. Brown, Boise State University
  • Alexandra E. Oxford, Boise State University
  • Brad E. Morrison, Boise State University
  • Eric J. Hayden, Boise State University
  • Troy T. Rohn, Boise State University
Document Type
Article
Publication Date
1-1-2019
Disciplines
Abstract

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.

Comments

For a complete list of authors, please see article.

Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Pollock, Tanner B.; Mack, Jacob M.; Isho, Noail F.; Brown, Raquel J.; Oxford, Alexandra E.; Morrison, Brad E.; Hayden, Eric J.; and Rohn, Troy T. (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, 2019, 5123565-1 - 5123565-13. http://dx.doi.org/10.1155/2019/5123565