Brief Description:
Stroke is the third leading cause of death in the United States. About 137,000 Americans die of stroke every year. Stroke can cause death or significant disability, such as paralysis, speech difficulties, and emotional problems. A stroke is an interruption of the blood supply to any part of the brain, causing hypoxia conditions in neurons and other cell types in the brain. The hypoxia-Inducible-Factor-1-α (HIF-1α) plays a critical role in sculpting the cellular transcriptional response to hypoxia. While moderate levels of hypoxia stimulate HIF-1α dependant adaptive gene expression, excessive hypoxic stress triggers a latent HIF-1α dependent pro-apoptotic program. The researchers discovered that MAPK phosphatase 1 (MKP1) is involved in the pathogenesis of stroke by altering the signaling behavior of transcription factors activated by hypoxia. In addition, they discovered that MKP-1 activation enhances HIF-1α pro-apoptotic signaling through activation of a site specific cleavage.
Applications:
Developing novel treatments for stroke based on compounds that block MKP-1 activity and/or compounds that inhibit the cleavage of HIF-1α.
Advantages:
Novel target pathway which may produce several different therapeutic compounds.