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The brain heme oxygenase/biliverdin reductase system as a target in drug research and development

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EXPERT OPINION ON THERAPEUTIC TARGETS
卷 26, 期 4, 页码 361-374

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TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2022.2052848

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carbon monoxide; drug research and development; heme oxygenase; nervous system; neurodegeneration

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This article explores the role of the HO/BVR system in heme metabolism and discusses the neuroprotective potential of drugs targeting HO-1. However, there are currently no drugs available that specifically target HO-1 or BVR.
Introduction The heme oxygenase/biliverdin reductase (HO/BVR) system is involved in heme metabolism. The inducible isoform of HO (HO-1) and BVR both exert cytoprotective effects by enhancing cell stress response. In this context, some xenobiotics, which target HO-1, including herbal products, behave as neuroprotectants in several experimental models of neurodegeneration. Despite this, no drug having either HO-1 or BVR as a main target is currently available. Areas covered After a description of the brain HO/BVR system, the paper analyzes the main classes of drugs acting on the nervous system, with HO as second-level target, and their neuroprotective potential. Finally, the difficulties that exist for the development of drugs acting on HO/BVR and the possible ways to overcome these hurdles are examined. Expert opinion Although the limited clinical evidence has restricted the translational research on the HO/BVR system, mainly because of the dual nature of its by-products, there has been growing interest in the therapeutic potential of these enzymes. Scientists should boost the translational research on the HO/BVR system which could be supported by the significant evidence provided by preclinical studies.

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