Heme oxygenase-1: transducer of pathological brain iron sequestration under oxidative stress.
Mechanisms responsible for the pathological deposition of redox-active brain iron in human neurological disorders remain incompletely understood. Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that degrades heme to biliverdin, free iron, and carbon monoxide. In this chapter, we review evidence that (1) HO-1 is overexpressed in CNS tissues affected by Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and other degenerative and nondegenerative CNS diseases; (2) the pro-oxidant effects of dopamine, hydrogen peroxide, beta-amyloid, and proinflammatory cytokines stimulate HO-1 expression in some of these conditions; and (3) upregulation of HO-1 in astrocytes exacerbates intracellular oxidative stress and promotes sequestration of nontransferrin-derived iron by the mitochondrial compartment. A model is presented implicating glial HO-1 induction as a "final common pathway" leading to pathological iron sequestration and mitochondrial insufficiency in a host of human CNS disorders.
Schipper
Hyman M
HM
Center for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. hyman.schipper@mcgill.ca
D001253:Astrocytes / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*
D008565:Membrane Proteins; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1