Hypoxia inducible factor prolyl hydroxylases as targets for neuroprotection by "antioxidant" metal chelators: From ferroptosis to stroke.

Hypoxia inducible factor prolyl hydroxylases as targets for neuroprotection by "antioxidant" metal chelators: From ferroptosis to stroke.
Free Radic Biol Med. 2013 Jan 31;
Authors: Speer RE, Karuppagounder SS, Basso M, Sleiman S, Kumar A, Brand D, Smirnova N, Gazaryan I, Khim SJ, Ratan RR
Abstract
Neurologic conditions including stroke, Alzheimer's disease, Parkinson's disease and Huntington's disease are leading causes of death and long-term disability in the United States, and efforts to develop novel therapeutics for these conditions have historically had poor success in translating from bench to bedside. Hypoxia Inducible Factor-1alpha (HIF-1α) mediates a broad, evolutionarily conserved, endogenous adaptive program to hypoxia, and manipulation of components of the HIF pathway are neuroprotective in a number of human neurological diseases and experimental models. In this review, we discuss molecular components of one aspect of hypoxic adpatation in detail, and provide perspective on which targets within this pathway appear to be ripest for preventing and repairing neurodegeneration. Further, we highlight the role of HIF prolyl hydroxylases as emerging targets for the salutary effects of metal chelators on ferroptosis in vitro as well in animal models of neurological diseases.
PMID: 23376032 [PubMed - as supplied by publisher]

Source: Free Radical Biology and Medicine - January 31, 2013 Category: Biology Authors: Speer RE, Karuppagounder SS, Basso M, Sleiman S, Kumar A, Brand D, Smirnova N, Gazaryan I, Khim SJ, Ratan RR Tags: Free Radic Biol Med Source Type: research