title: Impaired hypoxic tolerance in APP23 mice: a dysregulation of neuroprotective globin levels.
abstract: Although neuroglobin confers neuroprotection against Alzheimer's disease (AD) pathology, its expression becomes downregulated in late-stage AD. Here, we provide evidence that indicates that this decrease is associated with the AD-linked angiopathy. While wild-type mice of different ages show upregulated cerebral neuroglobin expression upon whole-body hypoxia, APP23 mice exhibit decreased cerebral transcription of neuroglobin. Interestingly, transcription of cytoglobin, whose involvement in amyloid pathology still needs to be elucidated, follows a similar pattern. To further unravel the underlying mechanism, we examined the expression levels of the RE-1-silencing transcription factor (REST/NRSF) after identifying a recognition site for it in the regulatory region of both globins. Neuroglobin-cytoglobin-REST/NRSF expression correlations are detected mainly in the cortex. This raises the possibility of REST/NRSF being an upstream regulator of these globins.
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Zoë P
authors.initials: ZP
authors.lastname: Van Acker
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Evi
authors.initials: E
authors.lastname: Luyckx
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Van Leuven
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Geuens
authors.affiliation: Laboratory of Neurochemistry & Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.|Alzheimer Research Center, Department of Neurology, University of Groningen, the Netherlands.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Laboratory of Neurochemistry & Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.|Alzheimer Research Center, Department of Neurology, University of Groningen, the Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D015687:Cell Hypoxia; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism*; D000078842:Cytoglobin; D004195:Disease Models, Animal; D015536:Down-Regulation; D005625:Frontal Lobe / Q000378:metabolism; D005914:Globins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000078787:Neuroglobin; D012097:Repressor Proteins / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D016564:Amyloid beta-Protein Precursor; D000078842:Cytoglobin; D005914:Globins; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C545487:APP protein, human; C000627265:CYGB protein, human; C000627267:Cygb protein, mouse
keywords: APP23; REST/NRSF; cytoglobin; hypoxia; neuroglobin