title: The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment.
abstract: Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer's disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress. HIF-1 also improves cerebral blood flow which opposes the toxicity of hypoxia. Increased HIF-1 activity and/or expression of HIF-1 target genes, such as those involved in glycolysis or vascular flow, may be an early adaptation to the oxidative stressors that characterize MCI pathology. The molecular events that constitute this early adaptation are likely neuroprotective, and might mitigate cognitive decline or the onset of full-blown AD. On the other hand, prolonged or overwhelming stressors can convert HIF-1 into an activator of cell death through agents such as Bnip3, an event that is more likely to occur in late MCI or advanced Alzheimer's dementia.
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Osigbemhe
authors.initials: O
authors.lastname: Iyalomhe
authors.affiliation: Department of Hematology/BMT, University of Utah School of Medicine, 30 N Medical Dr, Salt Lake City, UT, 84132, USA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Swierczek
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Ngozi
authors.initials: N
authors.lastname: Enwerem
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Yuanxiu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Monica O
authors.initials: MO
authors.lastname: Adedeji
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Allard
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Oyonumo
authors.initials: O
authors.lastname: Ntekim
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Sheree
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Division of Endovascular Surgery, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Kakra
authors.initials: K
authors.lastname: Hughes
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA.|Human Genome Center, Howard University, 2041 Georgia Ave NW, Washington, DC, 20060, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Kurian
authors.affiliation: Geriatrics Division, Department of Medicine, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC, 20060, USA. Tobisesan@howard.edu.|Howard University Clinical Research Unit (GHUCCTS CTSA), 2041 Georgia Ave, NW, Washington, DC, 20060, USA. Tobisesan@howard.edu.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Obisesan
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008568:Memory
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Alzheimer’s disease; Glucose; Glycolysis; Hypoxia-inducible factor 1; Inflammation; Mild cognitive impairment; Reactive oxygen species