Editorial [ Advances in Heme Oxygenase Research as a Potential Therapeutic Strategy Executive Editor: M.J. Alcaraz]

In 2003, the issue of Current Pharmaceutical Design entitled “Modulation of heme oxygenase-1 as a therapeutic target” presented six papers focused on the role and interest of heme oxygenase(HO)-1 modulation in human disease. This topic has generated significant interest in the last years leading to a growing number of publications. The purpose of this issue of Current Pharmaceutical Design is to highlight studies examining novel aspects of HO. These are important observations and point to fruitful areas for future research. All of these papers provide useful information to consider when assessing treatment strategies in human disease. By sharpening our current knowledge about the role of HO, we can better target specific interventions to a number of conditions. This issue opens with papers reporting research on HO as a therapeutic target in relevant diseases affecting metabolism, blood vessels and the central nervous system. The first article by prof. Abraham [1] describes the protective role of HO-1 in animal models of diabetes and obesity. Enhanced HO-1 expression and activity may be considered the primary defense against the deleterious effects of diabetes, metabolic syndrome and obesity. The second article by Dr. Chung [2] summarizes recent studies on HO-1 and its possible utility as a treatment for vascular diseases. Carbon monoxide is produced by HO activity and plays a protective role in vascular homeostasis, including the regulation of nitric oxide- and H2Sproducing enzymes that may be involved in either vascular protection or vascular injury. In the third article, Dr. Cuadrado [3] examines the role of HO-1 in redox homeostasis in the brain and neuroprotection. Pharmacological modulation of HO-1 has shown promising results in models of Alzheimer's, Parkinson's and of infectious diseases, such as malaria. This theme is continued by Prof. Parfenova, [4] who focuses on the functions of the constitutive isozyme, HO-2. Pharmacological inhibition or gene deletion of this enzyme in the brain exacerbates oxidative stress induced by seizures, glutamate, and inflammatory cytokines, and causes cerebral vascular injury, whereas the end products of HO-catalyzed heme degradation have cytoprotective functions. Next, Dr. Xia and co-workers [5] review the potential of HO-1 as a modulator in T cell-mediated immune processes. As a consequence, this enzyme may provide protection in asthma, organ transplantation rejection, inflammatory bowel disease and experimental autoimmune encephalomyelitis. The last two papers that are included in this issue make a contribution to the current knowledge about pharmacological interventions in the HO pathway. With the collaboration of Dr. Motterlini [6], we have discussed our own research on inflammation, HO-1 and carbon monoxidereleasing molecules including in vitro and in vivo studies. Finally, Dr. Ferrándiz [7] has summarised a number of pharmacological approaches to induce HO-1. Perhaps one result of this issue will be to stimulate future studies that address not only basic knowledge, but also therapeutic applications. The heme oxygenase pathway provides exciting areas for future intervention-oriented research. References [1] Abraham NG, Tsenovoy PL, McClung J, Drummond GS. Heme Oxygenase: A Target Gene for Anti-Diabetic and Obesity. Curr Pharm Des 2008; 14(5): 412-421. [2] Chung H-T, Pae H-O, Cha Y-N. Role of Heme Oxygenase-1 in Vascular Disease. Curr Pharm Des 2008; 14(5): 422-428. [3] Cuadrado A, Rojo AI. Heme Oxygenase-1 As A Therapeutic Target in Neurodegenerative Diseases and Brain Infections. Curr Pharm Des 2008; 14(5): 429-442. [4] Parfenova H, Leffler CW. Cerebroprotective Functions of HO-2. Curr Pharm Des 2008; 14(5): 443-453. [5] Xia ZW, Zhong WW, Meyrowitz JS, Zhang Z. The Role of Heme Oxygenase-1 in T Cell-Mediated Immunity: The All Encompassing Enzyme. Curr Pharm Des 2008; 14(5): 454-464. [6] Alcaraz MJ, Guillen MI, Ferrandiz ML, Megías J, Motterlini R. Carbon Monoxide-Releasing Molecules: A Pharmacological Expedient to Counteract Inflammation. Curr Pharm Des 2008; 14(5): 465-472. [7] Ferrándiz ML, Devesa I. Inducers of Heme Oxygenase-1. Curr Pharm Des 2008; 14(5): 473-486.