J. Neurochem. (2010) 112, 1–12.
Neurodegenerative diseases, generally characterized by a progressive deterioration in the structure and function of the brain, represent one of the world’s major unsolved health problems. Therefore, it is urgent to discover therapeutic targets for the design of effective strategies for the treatment of these diseases. Recent findings demonstrated that the induction of the hypoxia signaling pathway with the concomitant stabilization and transcriptional activation of the transcription factor hypoxia-inducible factor 1 (HIF-1) could mediate neuroprotective events. It has been shown that HIF-1 triggers the expression of genes involved in oxygen transport, glycolytic metabolism, angiogenesis, cell survival, apoptosis, and others processes that can interfere with cell survival. Here, we discuss the current knowledge pertaining to the regulation of HIF signaling pathway. The potential neuroprotective role of HIF-1 induction in cerebral ischemic stroke and Alzheimer’s, Parkinson’s, and Huntington’s diseases will be also discussed. The elucidation of the mechanisms involved in HIF-1-mediated neuroprotection could be important for the development of effective therapies to mitigate or prevent neurodegenerative diseases.