When the Brain Yearns for Oxygen

Nearly 30 years ago hypoxia-inducible factor (HIF) was described as a protein complex bound to regulatory DNA sequences termed hypoxia response elements because HIF binding induced transcription of the erythropoietin gene under hypoxia. However, it soon became clear that HIF is part of a ubiquitous cellular oxygen sensing system, which ensures finely tuned control of HIF abundance and activity in dependence of the cellular oxygen tension. For their discoveries of how cells sense and adapt to oxygen availability Gregg L. Semenza, William G. Kaelin Jr. and Sir Peter J. Ratcliffe received the Nobel Prize in Physiology or Medicine 2019. The Nobel laureates' pioneering work on cellular oxygen sensing has unraveled that HIF has numerous target genes reflecting its multiple functions in cellular metabolism and adaptation to different levels of oxygen. Importantly, HIF is also crucial for the development of the nervous system. HIF has an influence on different neural cell types regarding neurogenesis, maturation and apoptosis. Furthermore, HIF is involved in pathophysiological processes of the brain like stroke and Alzheimer's disease resulting in the development of HIF-related therapeutic approaches.