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Antioxid Redox Signal. 2014 Apr 10;20(11):1810-26. doi: 10.1089/ars.2013.5658. Epub 2014 Feb 28.

Heme oxygenase-1 as a target for drug discovery.

Author information

1
1 Université Paris-Est , UMR_S955, F-94000, Créteil, France .

Abstract

SIGNIFICANCE:

Heme oxygenase enzymes, which exist as constitutive (HO-2) and inducible (HO-1) isoforms, degrade heme to carbon monoxide (CO) and the bile pigment biliverdin. In the last two decades, substantial scientific evidence has been collected on the function of HO-1 in cell homeostasis, emphasizing these two important features: (i) HO-1 is a fundamental "sensor" of cellular stress and directly contributes toward limiting or preventing tissue damage; (ii) the products of HO-1 activity dynamically participate in cellular adaptation to stress and are inherently involved in the mechanisms of defence.

RECENT ADVANCES:

On the basis of its promising cytoprotective features, scientists have pursued the targeting of HO-1 as an attractive cellular pathway for drug discovery. Three different pharmacological approaches are currently being investigated in relation to HO-1, namely the use of CO gas, the development of CO-releasing molecules (CO-RMs), and small molecules possessing the ability to up-regulate HO-1 in cells and tissues. CRITICAL ISSUE: Studies on the regulation and amplification of the HO-1/CO pathway by selective pharmacological approaches may lead to the discovery of novel drugs for the treatment of a variety of diseases.

FUTURE DIRECTIONS:

In this review, we will discuss in detail the importance of pharmacologically manipulating the HO-1 pathway and its products for conferring protection against a variety of conditions that are characterized by oxidative stress and inflammation. We will also evaluate each of the strategic approaches being developed by considering their intrinsic advantages and disadvantages, which may have implications for their use as therapeutics in specific pathological conditions.

PMID:
24180608
DOI:
10.1089/ars.2013.5658
[Indexed for MEDLINE]

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