Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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The Protective Role of Heme Oxygenase-1 in Cerebral Ischemia

Author(s): Emmanuel Aztatzi-Santillan, Felipe Eduardo Nares-Lopez, Berenice Marquez-Valadez, Penelope Aguilera, Maria Elena Chanez-Cardenas.

Abstract:

Cerebral ischemia is one of the leading causes of death and disability in industrialized countries, with no curative treatments to date. Identification of potential targets and elucidation of their physiological role under stress conditions may give support to the development of drugs and strategies to contend with this pathology. In the last years, Heme oxygenase- 1 (HO-1) has been recognized by many groups as a potential target in ischemic damage. HO-1 is the enzyme responsible for the conversion of the heme group to biliverdin, carbon monoxide and iron; a highly regulated cytoprotective enzyme able to respond to numerous chemical or physical stressors, many of which decrease oxygen availability and generate oxidative stress. The disruption of HO-1 activity has been widely associated with a bad outcome in many disorders, and a protective role through its heme catabolism products has been observed in transplantation, cardiac ischemia, limb ischemia/reperfusion and different alterations that involve ischemia and reperfusion events. Here, we review recent reports supporting the protective role of HO-1 in cerebral ischemia. Results on the endogenous HO-1 response, overexpression of HO-1 and compounds that reduce ischemic damage through the induction of HO-1 in cerebral ischemia in in vivo and in vitro models are analyzed.

Keywords: Cerebral ischemia, heme-oxygenase -1, neuroprotection, oxidative stress, biliverdin, cytoprotective, heme-oxygenase -1,, homeostasis, glutamate, aspartate, apoptosis, thrombolytics, ischemic preconditioning (IP), myoglobins, cytochromes, catalases, pro-oxidant molecule (b-type heme), bilirubin, hyperoxia, hyperthermia, Activator protein 1 (AP-1), NF-E2 related factor (Nrf2), hypoxia inducible factor-1, mitogenactivated protein kinases (MAPK), phosphatidylinositol 3-kinase (PI3K), miocardial infarction, atherosclerosis, restenosis, endotoxin shock, sepsis, xenograft, hippocampus, striatum, bulb, cerebellum, middle cerebral artery occlusion (MCAO), neocortex, amygdala, extradural compression (EC), Goto-Kakizaki (GK) diabetic rats, hyperglycemia, lipopolysaccharide (LPS), protoporphyrin IX, Prostaglandin E1 (PGE1), photothrombosis, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA), oxygen glucose deprivation (OGD), Sulphoraphane (SFP), broccoli, Naphthoquinone plumbagin (PL), Thioredoxin reductase, actinomycin D, Hemopexin (HPX), vascular cell adhesion molecule-1 (VCAM-1), iron chelators

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Article Details

VOLUME: 10
ISSUE: 4
Year: 2010
Page: [310 - 316]
Pages: 7
DOI: 10.2174/187152410793429764
Price: $58