Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Hypoxia is one of the most common pathological conditions, which can be induced by multiple events, including ischemic injury, trauma, inflammation, tumors, etc. The body's adaptation to hypoxia is a highly important phenomenon in both health and disease. Most cellular responses to hypoxia are associated with a family of transcription factors called hypoxia-inducible factors (HIFs), which induce the expression of a wide range of genes that help cells adapt to a hypoxic environment. Basic mechanisms of adaptation to hypoxia, and particularly HIF functions, have being extensively studied over recent decades, leading to the 2019 Nobel Prize in Physiology or Medicine. Based on their pivotal physiological importance, HIFs are attracting increasing attention as a new potential target for treating a large number of hypoxia-associated diseases. Most of the experimental work related to HIFs has focused on roles in the liver and kidney. However, increasing evidence clearly demonstrates that HIF-based responses represent an universal adaptation mechanism in all tissue types, including the central nervous system (CNS). In the CNS, HIFs are critically involved in the regulation of neurogenesis, nerve cell differentiation, and neuronal apoptosis. In this mini-review, we provide an overview of the complex role of HIF-1 in the adaptation of neurons and glia cells to hypoxia, with a focus on its potential involvement into various neuronal pathologies and on its possible role as a novel therapeutic target.