A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells

Authors

Tanner B. Pollock, Boise State UniversityFollow
Jacob M. Mack, Boise State University
Noail F. Isho, Boise State University
Raquel J. Brown, Boise State UniversityFollow
Alexandra E. Oxford, Boise State UniversityFollow
Brad E. Morrison, Boise State UniversityFollow
Eric J. Hayden, Boise State UniversityFollow
Troy T. Rohn, Boise State UniversityFollow

Document Type

Article

Publication Date

2019

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 (nApoE4_1-151) 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 nApoE4_1-151. The results indicated that nApoE4_1-151 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 nApoE4_1-151 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 nApoE4_1-151 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.

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Publication 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