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Center for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Department of Neurology and Neurosurgery, and Department of Medicine (Geriatrics), McGill University, Montreal, Quebec, Canada
Address for correspondence: Hyman M. Schipper, Center for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, 3755 Côte Ste-Catherine Road, Montreal, Quebec H3T 1E2, Canada. Voice: 514-340-8260; fax: 514-340-7502. hyman.schipper{at}mcgill.ca Ann. N.Y. Acad. Sci. 1012: 84-93 (2004).
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, b-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.
Key Words: Alzheimer's disease • amyloid • astrocyte • cytokines • dopamine • heme oxygenase-1 • iron • mitochondria • multiple sclerosis • oxidative stress • Parkinson's disease This article has been cited by other articles:
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