A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells
| Autor: | Ryan Day, Alexandra E. Oxford, Raquel J. Brown, Eric J. Hayden, Jacob M Mack, Brad E. Morrison, Noail F Isho, Troy T. Rohn, Tanner B Pollock |
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| Rok vydání: | 2019 |
| Předmět: |
Aging
Article Subject medicine.medical_treatment Apolipoprotein E4 Inflammation Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Gene expression medicine Animals Humans lcsh:QH573-671 Cells Cultured 030304 developmental biology 0303 health sciences Microglia Chemistry lcsh:Cytology Promoter Cell Biology General Medicine Peptide Fragments Cell biology medicine.anatomical_structure Cytokine Gene Expression Regulation Astrocytes Cytokines Tumor necrosis factor alpha medicine.symptom Nucleus 030217 neurology & neurosurgery Transcription Factors Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2019 (2019) |
| ISSN: | 1942-0994 |
| Popis: | 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 nApoE41-151leads 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 nApoE41-151resulted 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 nApoE41-151with the TNFαpromoter region. Collectively, these data identify a novel gene-regulatory pathway involving CXorf56 that may link apoE4 to microglia activation and inflammation associated with AD. |
| Databáze: | OpenAIRE |
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