Physiological functions and the current research in clinical diseases of neuroglobin

doi:10.3877/cma.j.issn.2095-123X.2025.04.009

Abstract

Abstract:

Neuroglobin (Ngb) is mainly present in neural tissue and is an endogenous neuroprotective molecule that can counteract hypoxic-ischemia and oxidative stress-induced injury in cultured neurons and animals. Its gene and protein expression under hypoxic conditions and has protective effect on cell survival, significantly protecting the heart and brain from hypoxia, ischaemia and oxidative stress-induced injury, whereas reduced levels of Ngb lead to increased tissue damage. Therefore, the strategy of upregulating endogenous Ngb expression has potential therapeutic prospects. This review focuses on the structure, physiological functions and protective mechanisms of Ngb, aiming to provide new ideas for the treatment of various clinical diseases.

Key words: Neuroglobin, Physiological function, Neuroprotection

Min Cheng, Yafeng Wu, Yating Han, Huailian Guo. Physiological functions and the current research in clinical diseases of neuroglobin[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(04): 246-250.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhnkjbykfzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-123X.2025.04.009

https://zhnkjbykfzz.cma-cmc.com.cn/EN/Y2025/V15/I04/246

References 49

[1]	Fiocchetti M, Cipolletti M, Brandi V, et al. Neuroglobin and friends[J]. J Mol Recognit, 2017, 30(12): e2654. DOI: 10.1002/jmr.2654.
[2]	Simon R. Neuroglobin: neuroprotection and neurogenesis[J]. Neurosci Lett, 2013, 549: 1-2. DOI: 10.1016/j.neulet.2013.05.016.
[3]	Ascenzi P, di Masi A, Leboffe L, et al. Neuroglobin: from structure to function in health and disease[J]. Mol Aspects Med, 2016, 52: 1-48. DOI: 10.1016/j.mam.2016.10.004.
[4]	Couture M, Burmester T, Hankeln T, et al. The heme environment of mouse neuroglobin. Evidence for the presence of two conformations of the heme pocket[J]. J Biol Chem, 2001, 276(39): 36377-36382. DOI: 10.1074/jbc.M103907200.
[5]	Guidolin D, Tortorella C, Marcoli M, et al. Neuroglobin, a factor playing for nerve cell survival[J]. Int J Mol Sci, 2016, 17(11): 1817. DOI: 10.3390/ijms17111817.
[6]	曹聪，张蓓. 脑红蛋白生物功能及作用机制研究进展[J]. 脑与神经疾病杂志, 2018, 26(7): 454-456.
[7]	Yu Z, Xu J, Liu N, et al. Mitochondrial distribution of neuroglobin and its response to oxygen-glucose deprivation in primary-cultured mouse cortical neurons[J]. Neuroscience, 2012, 218: 235-242. DOI: 10.1016/j.neuroscience.2012.05.054.
[8]	Yu Z, Zhang Y, Liu N, et al. Roles of neuroglobin binding to mitochondrial complex III subunit cytochrome c1 in oxygen-glucose deprivation-induced neurotoxicity in primary neurons[J]. Mol Neurobiol, 2016, 53(5): 3249-3257. DOI: 10.1007/s12035-015-9273-4.
[9]	Semenova MA, Chertkova RV, Kirpichnikov MP, et al. Molecular interactions between neuroglobin and cytochrome c: possible mechanisms of antiapoptotic defense in neuronal cells[J]. Biomolecules, 2023, 13(8): 1233. DOI: 10.3390/biom13081233.
[10]	Exertier C, Montemiglio LC, Freda I, et al. Neuroglobin, clues to function and mechanism[J]. Mol Aspects Med, 2022, 84: 101055. DOI: 10.1016/j.mam.2021.101055.
[11]	杨立涛，刘爽，于常海. 脑红蛋白和细胞红蛋白:携氧蛋白质家族2个新成员[J]. 中国生物化学与分子生物学报, 2006, 22(4): 267-271. DOI: 10.3969/j.issn.1007-7626.2006.04.001.
[12]	Yu Z, Liu N, Liu J, et al. Neuroglobin, a novel target for endogenous neuroprotection against stroke and neurodegenerative disorders[J]. Int J Mol Sci, 2012, 13(6): 6995-7014. DOI: 10.3390/ijms13066995.
[13]	Jin K, Mao XO, Xie L, et al. Neuroglobin protects against nitric oxide toxicity[J]. Neurosci Lett, 2008, 430(2): 135-137. DOI: 10.1016/j.neulet.2007.10.031.
[14]	Brittain T, Skommer J, Henty K, et al. A role for human neuroglobin in apoptosis[J]. IUBMB Life, 2010, 62(12): 878-885. DOI: 10.1002/iub.405.
[15]	Manganelli V, Salvatori I, Costanzo M, et al. Overexpression of neuroglobin promotes energy metabolism and autophagy induction in human neuroblastoma SH-SY5Y cells[J]. Cells, 2021, 10(12): 3394. DOI: 10.3390/cells10123394.
[16]	Gao WJ, Mo C, Feng W, et al. Research on the effects of neuroglobin on ferroptosis in the nerve cells[J]. Chinese Medicine and Natural Products, 2023, 3(3): 133-142. DOI: 10.1055/s-0043-1773796.
[17]	Van Acker ZP, Van Raemdonck GA, Logie E, et al. Connecting the dots in the neuroglobin-protein interaction network of an unstressed and ferroptotic cell death neuroblastoma model[J]. Cells, 2019, 8(8): 873. DOI: 10.3390/cells8080873.
[18]	Wang X, Liu J, Zhu H, et al. Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia[J]. Stroke, 2008, 39(6): 1869-1874. DOI: 10.1161/strokeaha.107.506022.
[19]	Sun Y, Jin K, Mao XO, et al. Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury[J]. Proc Natl Acad Sci USA, 2001, 98(26): 15306-15311. DOI: 10.1073/pnas.251466698.
[20]	Jin K, Mao Y, Mao X, et al. Neuroglobin expression in ischemic stroke[J]. Stroke, 2010, 41(3): 557-559. DOI: 10.1161/strokeaha.109.567149.
[21]	Lin Y, Fang L, Xue XH, et al. Association between Ngb polymorphisms and ischemic stroke in the southern Chinese Han population[J]. BMC Med Genet, 2008, 9: 110. DOI: 10.1186/1471-2350-9-110.
[22]	Chen XQ, Qin LY, Zhang CG, et al. Presence of neuroglobin in cultured astrocytes[J]. Glia, 2005, 50(2): 182-186. DOI: 10.1002/glia.20147.
[23]	Blanco S, Martínez-Lara E, Siles E, et al. New strategies for stroke therapy: nanoencapsulated neuroglobin[J]. Pharmaceutics, 2022, 14(8): 1737. DOI: 10.3390/pharmaceutics14081737.
[24]	Shang A, Zhou D, Wang L, et al. Increased neuroglobin levels in the cerebral cortex and serum after ischemia-reperfusion insults[J]. Brain Res, 2006, 1078(1): 219-226. DOI: 10.1016/j.brainres.2006.01.064.
[25]	李康，高晓虹，栗改云, 等. 脑红蛋白在增殖性糖尿病视网膜病变患者眼部及血清中表达的研究[J]. 眼科, 2017, 26(5): 323-327. DOI: 10.13281/j.cnki.issn.1004-4469.2017.05.008.
[26]	Hümmler N, Schneider C, Giessl A, et al. Acute hypoxia modifies regulation of neuroglobin in the neonatal mouse brain[J]. Exp Neurol, 2012, 236(1): 112-121. DOI: 10.1016/j.expneurol.2012.04.006.
[27]	Xue L, Chen H, Lu K, et al. Clinical significance of changes in serum neuroglobin and HIF-1α concentrations during the early-phase of acute ischemic stroke[J]. J Neurol Sci, 2017, 375: 52-57. DOI: 10.1016/j.jns.2017.01.039.
[28]	Liu N, Yu Z, Xiang S, et al. Transcriptional regulation mechanisms of hypoxia-induced neuroglobin gene expression[J]. Biochem J, 2012, 443(1): 153-164. DOI: 10.1042/bj20111856.
[29]	Shang A, Feng X, Wang H, et al. Neuroglobin upregulation offers neuroprotection in traumatic brain injury[J]. Neurol Res, 2012, 34(6): 588-594. DOI: 10.1179/1743132812y.0000000052.
[30]	Zhao S, Yu Z, Zhao G, et al. Neuroglobin-overexpression reduces traumatic brain lesion size in mice[J]. BMC Neurosci, 2012, 13: 67. DOI: 10.1186/1471-2202-13-67.
[31]	刘凤民，左苗英. 血清NGB、BNP水平与颅脑损伤患者伤情严重程度及预后的相关性研究[J]. 国际神经病学神经外科学杂志, 2021, 48(5): 443-446. DOI: 10.16636/j.cnki.jinn.1673-2642.2021.05.007.
[32]	Sun F, Mao X, Xie L, et al. Neuroglobin protein is upregulated in Alzheimer's disease[J]. J Alzheimers Dis, 2013, 36(4): 659-663. DOI: 10.3233/jad-130323.
[33]	Liu N, Yu Z, Xun Y, et al. Amyloid-β25-35 upregulates endogenous neuroprotectant neuroglobin via NFκB activation in vitro[J]. J Alzheimers Dis, 2018, 64(4): 1163-1174. DOI: 10.3233/jad-180163.
[34]	de Vidania S, Palomares-Perez I, Frank-García A, et al. Prodromal Alzheimer's disease: constitutive upregulation of neuroglobin prevents the initiation of Alzheimer's pathology[J]. Front Neurosci, 2020, 14: 562581. DOI: 10.3389/fnins.2020.562581.
[35]	Fiocchetti M, Cracco P, Montalesi E, et al. Neuroglobin and mitochondria: the impact on neurodegenerative diseases[J]. Arch Biochem Biophys, 2021, 701: 108823. DOI: 10.1016/j.abb.2021.108823.
[36]	Sun Y, Jin K, Mao XO, et al. Effect of aging on neuroglobin expression in rodent brain[J]. Neurobiol Aging, 2005, 26(2): 275-278. DOI: 10.1016/j.neurobiolaging.2004.03.006.
[37]	Khan AA, Mao XO, Banwait S, et al. Neuroglobin attenuates beta-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo[J]. Proc Natl Acad Sci USA, 2007, 104(48): 19114-19119. DOI: 10.1073/pnas.0706167104.
[38]	Li Y, Dai YB, Sun JY, et al. Neuroglobin attenuates beta amyloid-induced apoptosis through inhibiting caspases activity by activating PI3K/Akt signaling pathway[J]. J Mol Neurosci, 2016, 58(1): 28-38. DOI: 10.1007/s12031-015-0645-z.
[39]	李康，李静，高晓虹. 脑红蛋白在眼科的研究现状[J]. 国际眼科纵览, 2016, 40(2): 140-144. DOI: 10.3760/cma.j.issn.1673-5803.2016.02.015.
[40]	Wei X, Yu Z, Cho KS, et al. Neuroglobin is an endogenous neuroprotectant for retinal ganglion cells against glaucomatous damage[J]. Am J Pathol, 2011, 179(6): 2788-2797. DOI: 10.1016/j.ajpath.2011.08.015.
[41]	Roberts PA, Gaffney EA, Luthert PJ, et al. Retinal oxygen distribution and the role of neuroglobin[J]. J Math Biol, 2016, 73(1): 1-38. DOI: 10.1007/s00285-015-0931-y.
[42]	刘琼，于健，陈林江. 脑红蛋白在糖尿病大鼠视网膜病变发展中的表达变化[J]. 中国实用医药, 2019, 14(13): 192-194. DOI: 10.14163/j.cnki.11-5547/r.2019.13.102.
[43]	Solar Fernandez V, Marino M, Fiocchetti M. Neuroglobin in retinal neurodegeneration: a potential target in therapeutic approaches[J]. Cells, 2021, 10(11): 3200. DOI: 10.3390/cells10113200.
[44]	Qin H, Guo Y, Zhang C, et al. The expression of neuroglobin in astrocytoma[J]. Brain Tumor Pathol, 2012, 29(1): 10-16. DOI: 10.1007/s10014-011-0066-9.
[45]	Zhang J, Lan SJ, Liu QR, et al. Neuroglobin, a novel intracellular hexa-coordinated globin, functions as a tumor suppressor in hepatocellular carcinoma via Raf/MAPK/Erk[J]. Mol Pharmacol, 2013, 83(5): 1109-1119. DOI: 10.1124/mol.112.083634.
[46]	Oleksiewicz U, Daskoulidou N, Liloglou T, et al. Neuroglobin and myoglobin in non-small cell lung cancer: expression, regulation and prognosis[J]. Lung Cancer, 2011, 74(3): 411-418. DOI: 10.1016/j.lungcan.2011.05.001.
[47]	Luyckx E, Van Acker ZP, Ponsaerts P, et al. Neuroglobin expression models as a tool to study its function[J]. Oxid Med Cell Longev, 2019, 2019: 5728129. DOI: 10.1155/2019/5728129.
[48]	Cai H, Zheng S, Cai B, et al. Neuroglobin as a novel biomarker for predicting poor outcomes in aneurysmal subarachnoid hemorrhage[J]. World Neurosurg, 2018, 116: e258-e265. DOI: 10.1016/j.wneu.2018.04.184.
[49]	张菲菲，程艳伟，于敏敏, 等. 大鼠癫痫持续状态后海马组织各区脑红蛋白表达的实验研究[J]. 癫痫杂志, 2017, 3(3): 217-222. DOI: 10.7507/2096-0247.20170033.

Please choose a citation manager

Content to export