Heme Oxygenase 1 in the Nervous System: Does It Favor Neuronal Cell Survival or Induce Neurodegeneration?

Abstract

Heme oxygenase 1 (HO-1) up-regulation is recognized as a pivotal mechanism of cell adaptation to stress. Under control of different transcription factors but with a prominent role played by Nrf2, HO-1 induction is crucial also in nervous system response to damage. However, several lines of evidence have highlighted that HO-1 expression is associated to neuronal damage and neurodegeneration especially in Alzheimer’s and Parkinson’s diseases. In this review, we summarize the current literature regarding the role of HO-1 in nervous system pointing out different molecular mechanisms possibly responsible for HO-1 up-regulation in nervous system homeostasis and neurodegeneration.

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

“…Interestingly, recent evidence in a rat model of MCAO established that intraperitoneal administration of biliverdin significantly reduces the infarct size by modulating microRNA-mRNA network (Zou et al, 2019). It is important to note that at the level of the nervous system, up-regulation of HMOX1 can be both protective and damaging as reviewed recently (Nitti et al, 2018), but the role played by HMOX1 derived bilirubin in neurons and non-neuronal cells in neuroprotection has been highlighted (Hung et al, 2010).…”

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

“…Furthermore, BDNF knockout mice showed reduced DA D3 receptor expression [27]. BDNF protects hippocampal neurons from oxidative damage due to injury and inflammation via heme oxygenase (HO-1) induction, which is achieved by inducing Nrf2 nuclear translocation via activation of the Ras-MAPK and PI3K-AKT signaling pathways [28,29] (Figure 2). These studies suggest that the reduction in BDNF expression is linked to pathological alterations of the DAergic neurons in the SNpc.…”

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

“…HO-1 can be induced by oxidative stress, low oxygen tension and gaseous molecules, such as nitric oxide (NO) and CO [10]. The relationship between HO and adult neural circuit regeneration seems to be complex [18]. Long-term overexpression of HO-1 may be detrimental for cognitive ability in the rodent Alzheimer's disease (AD) model [15,19].…”

“…Abnormal patterns of iron deposition caused by long-term glial-HO-1 overexpression can cause cytotoxicity in astrocytes via mitochondrial dysfunction, leading to neuronal toxicity [15]. In contrast, transient HO-1 activation via CO treatment may be beneficial for regeneration in acute ischemic CNS injury [8,9,18,[20][21][22].…”