Ngb, short for neuroglobin, is a hemoprotein predominantly expressed in the brain and belongs to the globin family. It has a high affinity for oxygen and plays crucial roles in regulating O₂ homeostasis, oxidative stress, and acts as a neuroprotector [1,2,3,5,8]. It may be involved in multiple metabolic pathways such as ionic homeostasis maintenance, energy metabolism, mitochondrial function, and cell signaling [5]. Genetic models are valuable for studying its functions.

In severe aneurysmal subarachnoid hemorrhage (aSAH) patients, serum Ngb level was positively correlated with cerebral microdialysis parameters and brain tissue oxygen tension, and higher Ngb levels were associated with poor functional outcome at 12 months and impairments in cognition, visual conceptualization, and frontal executive functions [1]. After spinal cord injury (SCI) in rats, the expression of Ngb in astrocytes increased first and then decreased, peaking at 14 days, suggesting its involvement in anti-oxidative stress injury in astrocytes [2]. Mn-TAT PTD-Ngb, a novel artificial recombinant protein, could attenuate oxidative injury by scavenging ROS and regulating redox signaling pathways, and also ameliorate inflammation by eliminating damaged mitochondria and activating the Nrf2-antioxidant signaling pathway [3,4]. Polydatin protected neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling [6]. In acute ischemic stroke patients undergoing intravenous thrombolysis, higher serum Ngb levels were an independent risk factor for early neurological deterioration and poor prognosis [7].

In conclusion, Ngb is essential for maintaining brain homeostasis, especially in conditions related to hypoxia, ischemia, and oxidative stress. Studies on Ngb, including those potentially using gene knockout or conditional knockout mouse models (although not explicitly detailed in the given references), contribute to understanding its role in diseases such as aSAH, SCI, and acute ischemic stroke, providing insights for potential therapeutic strategies.

References:

1. Ding, Chen-Yu, Kang, De-Zhi, Wang, Zi-Liang, Lin, Zhang-Ya, Gu, Jian-Jun. 2019. Serum Ngb (Neuroglobin) Is Associated With Brain Metabolism and Functional Outcome of Aneurysmal Subarachnoid Hemorrhage. In Stroke, 50, 1887-1890. doi:10.1161/STROKEAHA.119.025733. https://pubmed.ncbi.nlm.nih.gov/31182001/

2. Liu, Zengqiang, Song, Bo. 2022. Expression Pattern of Ngb in Astrocytes after Spinal Cord Injury and the Clinical Significance. In Cellular and molecular biology (Noisy-le-Grand, France), 67, 160-166. doi:10.14715/cmb/2021.67.6.22. https://pubmed.ncbi.nlm.nih.gov/35818200/

3. Zhang, Cui, Hao, Xuehui, Chang, Jiaying, Geng, Zhirong, Wang, Zhilin. 2019. Mn-TAT PTD-Ngb attenuates oxidative injury by an enhanced ROS scavenging ability and the regulation of redox signaling pathway. In Scientific reports, 9, 20103. doi:10.1038/s41598-019-56595-5. https://pubmed.ncbi.nlm.nih.gov/31882813/

4. Zhang, Cui, Yang, Ruirui, Hao, Xuehui, Geng, Zhirong, Wang, Zhilin. 2020. Mn-TAT PTD-Ngb ameliorates inflammation through the elimination of damaged mitochondria and the activation of Nrf2-antioxidant signaling pathway. In Biochemical pharmacology, 178, 114055. doi:10.1016/j.bcp.2020.114055. https://pubmed.ncbi.nlm.nih.gov/32470548/

5. Fiocchetti, Marco, Cipolletti, Manuela, Brandi, Valentina, Polticelli, Fabio, Ascenzi, Paolo. 2017. Neuroglobin and friends. In Journal of molecular recognition : JMR, 30, . doi:10.1002/jmr.2654. https://pubmed.ncbi.nlm.nih.gov/28707399/

6. Zhang, Huihui, Li, Yadan, Xun, Yu, Liu, Ning, Xiang, Shuanglin. 2021. Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling. In Molecular medicine reports, 25, . doi:10.3892/mmr.2021.12525. https://pubmed.ncbi.nlm.nih.gov/34751416/

7. Zhang, Lihong, Wang, Cui, Zhao, Manhong, Xu, Jianping, Li, Di. . Prognostic Values Serum Cav-1 and NGB Levels in Early Neurological Deterioration After Intravenous Thrombolysis in Patients with Acute Ischemic Stroke. In Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 29, 10760296231219707. doi:10.1177/10760296231219707. https://pubmed.ncbi.nlm.nih.gov/38092682/

8. García-García, Fabio, Acosta-Hernández, Mario Eduardo, Beltrán-Parrazal, Luis, Rodríguez-Alba, Juan Carlos. 2023. The Role of Neuroglobin in the Sleep-Wake Cycle. In Sleep science (Sao Paulo, Brazil), 16, e362-e367. doi:10.1055/s-0043-1772806. https://pubmed.ncbi.nlm.nih.gov/38196764/