The Heme Oxygenase/Biliverdin Reductase System in Human Health and Disease: New Molecular Insights and Therapeutic Targets

Dear Colleagues,

Heme oxygenase (HO) catalyzes the breakdown of heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), which is subsequently converted into bilirubin-IXα (BR) by biliverdin reductase-A (BVR). Two HO isoforms exist: HO-1, an inducible enzyme, and HO-2, which is constitutively expressed. HO-1 is strongly upregulated by free radicals and pro-inflammatory signals, reducing intracellular heme—a cytotoxic molecule under redox imbalance—and generating CO, a gaseous neuromodulator with cytoprotective functions. These properties have placed HO-1 at the center of intense research over recent decades.

Preclinical studies consistently associate HO-1 with neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and cerebral malaria, as well as cardiovascular, renal, metabolic diseases and cancer. Furthermore, many xenobiotics induce HO-1 and elicit protective effects, making this isoform an attractive target in drug R&D. In contrast, HO-2 research has progressed more slowly. Its role as a basal regulator of heme turnover and the limited evidence for its involvement in gaseous molecule sensing have limited interest in HO-2 clinical exploitation. BVR, once viewed merely as the enzyme producing BR, experienced renewed attention in the 2000s, when additional tyrosine and serine/threonine kinase functions were identified. Today, BVR is recognized as an important regulator of glucose metabolism, neurodegeneration, and immune responses.

This Special Issue of Biomolecules welcomes contributions exploring the HO/BVR system in health and disease, including new mechanistic insights and therapeutic opportunities.

Prof. Dr. Cesare Mancuso
Guest Editor

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