Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023:1438:33-36.
doi: 10.1007/978-3-031-42003-0_6.

Pro-survival Phenotype of HIF-1α: Neuroprotection Through Inflammatory Mechanisms

Michelle A Puchowicz  1   2 , Kehkashan Parveen  3 , Aarti Sethuraman  3 , Tauheed Ishrat  4 , Kui Xu  5 , Joseph LaManna  5
Affiliations
Review

Pro-survival Phenotype of HIF-1α: Neuroprotection Through Inflammatory Mechanisms

Michelle A Puchowicz et al. Adv Exp Med Biol. 2023.

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a major player in the oxygen sensor system as well as a transcription factor. HIF-1 is also associated in the pathogenesis of many brain diseases including Alzheimer's disease (AD), epilepsy and stroke. HIF-1 regulates the expression of many genes such as those involved in glycolysis, erythropoiesis, angiogenesis and proliferation in hypoxic condition. Despite several studies, the mechanism through which HIF-1 confers neuroprotection remains unclear, one of them is modulating metabolic profiles and inflammatory pathways. Characterization of the neuroprotective role of HIF-1 may be through its stabilization and the regulation of target genes that aid in the early adaptation to the oxidative stressors. It is interesting to note that mounting data from recent years point to an additional crucial regulatory role for hypoxia-inducible factors (HIFs) in inflammation. HIFs in immune cells regulate the production of glycolytic energy as well as innate immunity, pro-inflammatory gene expression, and mediates activation of pro-survival pathways. The present review highlights the contribution of HIF-1 to neuroprotection where inflammation is the crucial factor in the pathogenesis contributing to neural death. The potential mechanisms that contribute to neuroprotection as a result of the downstream targets of HIF-1α are discussed. Such mechanisms include those mediated through IL-10, an anti-inflammatory molecule involved in activating pro-survival signaling mechanisms via AKT/ERK and JAK/STAT pathways.

Keywords: HIF-1α; Neuroinflammation; Neuroprotection.

PubMed Disclaimer

References

    1. Semenza GL (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology 19:176–182 - DOI - PubMed
    1. Semenza GL (2011) Oxygen sensing, homeostasis, and disease. N Engl J Med 365(6):537–547 - DOI - PubMed
    1. Eltzschig HK, Carmeliet P (2011) Hypoxia and inflammation. N Engl J Med 364(7):656–665 - DOI - PubMed - PMC
    1. Crifo B, Taylor CT (2016) Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease. J Investig Med 64(2):369–375 - DOI - PubMed
    1. Shin DH, Li SH, Yang SW, Lee BL, Lee MK, M.K., Park J.W. (2009) Inhibitor of nuclear factor-kappaB alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxia-inducible factor 1alpha. FEBS J 276(13):3470–3480 - DOI - PubMed

Substances

LinkOut - more resources