Ngb, short for Neuroglobin, is a hemoprotein predominantly expressed in the brain. It belongs to the globin family and has a high affinity for oxygen. Ngb plays crucial roles in regulating O₂ homeostasis, oxidative stress, and acts as a neuroprotector, especially after ischemia/hypoxia events. It is involved in multiple metabolic pathways such as ionic homeostasis maintenance, energy metabolism, mitochondrial function, and cell signaling [6,10].

In severe aneurysmal subarachnoid hemorrhage (aSAH) patients, serum Ngb level is positively correlated with cerebral microdialysis parameters, brain tissue oxygen tension, and is associated with 12-month neurological outcomes. Higher Ngb levels are related to poor functional outcome and impairments in cognition, visual conceptualization, and frontal executive functions [1]. After spinal cord injury (SCI) in rats, Ngb expression in astrocytes first increases and then decreases, peaking at 14 days. It may be involved in anti-oxidative stress injury in astrocytes [2]. In the context of drug addiction, the selective dopamine D3 receptor antagonist NGB 2904 has potential in controlling motivation for drug-taking behavior or relapse [3]. Mn-TAT PTD-Ngb, a novel neuroprotective manganese porphyrin reconstituted metal protein, can attenuate oxidative injury through enhanced ROS scavenging and regulation of the redox signaling pathway [4]. It also ameliorates inflammation by eliminating damaged mitochondria and activating the Nrf2-antioxidant signaling pathway [5]. Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling [7]. In acute ischemic stroke patients undergoing intravenous thrombolysis, serum Ngb level is an independent risk factor for early neurological deterioration and poor prognosis [8]. Yeast-expressed Tat-NGB-His can protect hypoxia-induced injury of PC12 cells [9]. Also, Ngb immunoreactivity is related to the sleep-wake cycle in mammals [10].

In conclusion, Ngb is a key protein involved in multiple biological processes, especially in protecting the nervous system from hypoxic, ischemic, oxidative, and inflammatory insults. Its dysregulation is associated with various neurological and non-neurological diseases such as aSAH, SCI, drug addiction, and acute ischemic stroke. Understanding Ngb through these studies provides insights into potential biomarker discovery and therapeutic strategies for related diseases.