The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment

Osigbemhe Iyalomhe, Sabina Swierczek, Ngozi Enwerem, Yuanxiu Chen, Monica O. Adedeji, Joanne Allard, Oyonumo Ntekim, Sheree Johnson, Kakra Hughes, Philip Kurian, Thomas O. Obisesan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCellular and Molecular Neurobiology
DOIs
StateAccepted/In press - Nov 17 2016
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Glucose
  • Glycolysis
  • Hypoxia-inducible factor 1
  • Inflammation
  • Mild cognitive impairment
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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