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

• Published in: Expert opinion on therapeutic targets Vol. 26; no. 4; p. 361
• Main Author: Mancuso, Cesare
• Format: Journal Article
• Language: English
• Published: England 03-04-2022
• Subjects: Brain - metabolism; Heme Oxygenase (Decyclizing) - metabolism; Heme Oxygenase-1 - metabolism; Humans; Oxidoreductases Acting on CH-CH Group Donors - metabolism; heme oxygenase; carbon monoxide; neurodegeneration; nervous system; drug research and development
• ISSN: 1744-7631
• DOI: 10.1080/14728222.2022.2052848

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.
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.
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.