Roles of Heme Oxygenase-1 in Neuroinflammation and Brain Disorders

Abstract

The heme oxygenase (HO) system is believed to be a crucial mechanism for the nervous system under stress conditions. HO degrades heme to carbon monoxide, iron, and biliverdin. These heme degradation products are involved in modulating cellular redox homeostasis. The first identified isoform of the HO system, HO-1, is an inducible protein that is highly expressed in peripheral organs and barely detectable in the brain under normal conditions, whereas HO-2 is a constitutive protein that is highly expressed in the brain. Several lines of evidence indicate that HO-1 dysregulation is associated with brain inflammation and neurodegeneration, including Parkinson's and Alzheimer's diseases. In this review, we summarize the essential roles that the HO system plays in ensuring brain health and the molecular mechanism through which HO-1 dysfunction leads to neurodegenerative diseases and disruption of nervous system homeostasis. We also provide a summary of the herbal medicines involved in the regulation of HO-1 expression and explore the current situation regarding herbal remedies and brain disorders.

Keywords: Alzheimer’s disease; Parkinson’s disease; heme oxygenase; neurodegenerative diseases; neuroinflammation.

Figure 1

The amino acid alignment of HO. (A) Amino acid alignment of HO-1 and HO-2 in human. (B) The amino acid homology of HO-1 in humans, rat, and mice. Asterisks indicate common retention regions, meaning that the amino acids here are identical.

Figure 2

Schematic representation of the HO-1 regulation and its role in the procession of neurodegeneration and neuroprotection. In neurodegeneration, proinflammatory factors induce HO-1 expression via MAPKs, NF-κB, and AP-1 in glial cells. However, several herbal medicines induce HO-1 expression via Nrf2-dependent pathway in neuronal cells, indicating the major route of HO-1 induction for neuroprotective function. Thus, in brain, the final impact of upregulated HO-1 is depend on the stimulatory factors, the activated signaling pathways, and the stimulated cell-type.