Neuroglobin: From structure to function in health and disease. (December 2016)

• Record Type: Journal Article
• Authors: Ascenzi, Paolo; di Masi, Alessandra; Leboffe, Loris; Fiocchetti, Marco; Nuzzo, Maria Teresa; Brunori, Maurizio; Marino, Maria
• Is Part Of: Molecular aspects of medicine. Volume 52(2016)
• Page Start: 1
• Page End: 48
• Publication Date: 2016-12
• Subjects: Neuroglobin -- Structure -- Function -- Signaling -- Neuroprotection -- Neurodegeneration -- Cancer; αSyn α-synuclein -- Aβ amyloid β -- AD Alzheimer's disease -- Adgb androglobin -- AIF apoptotic inducing factor -- AMPK AMP-activated protein kinase -- APAF apoptotic protease activating factor -- APP amyloid β precursor protein -- Bcl B-cell lymphoma -- BH Bcl-2 homology -- CNS central nervous system -- CREB cAMP response element binding -- Cygb cytoglobin -- DFX deferoxamine -- E2 17β-estradiol -- EPO erythropoietin -- ERα estrogen receptor α -- ERβ estrogen receptor β -- ERE estrogen response element -- ERK extracellular receptor kinase -- Etfα electron-transferring flavoprotein α-subunit -- flavoHb flavo-hemoglobin -- GbE globin E -- GbX globin X -- GbY globin Y -- GDI guanosine nucleotide dissociation inhibitor -- Hb hemoglobin -- HGbI Hell's Gate globin I -- HIF-1 hypoxia inducible factor-1 -- HTT huntingtin -- IOP intraoptical pressure -- IPC ischemic preconditioning -- NK c-Jun NH2-terminal kinases -- LVD large-artery atherosclerosis -- MAP mitogen-activated protein -- Mb myoglobin -- mPTP mitochondrial permeability transition pore -- N2a Neuro-2a -- Ngb neuroglobin -- ND neurodegenerative diseases -- NF-κB nuclear factor κ-light-chain enhancer of activated B cells -- NMDA N-methyl-D-aspartate -- NMR nuclear magnetic resonance -- NRSE neuron-restrictive silencer element -- NRSF neuron-restrictive silencer factor -- O2 oxygen -- O2●− superoxide -- OGD oxygen glucose deprivation -- PC12 pheochromocytoma cells -- PD Parkinson's disease -- PI3K phosphatidyl inositol 3-kinase -- RNS reactive nitrogen species -- ROS reactive oxygen species -- SNP single nucleotide polymorphism -- Sp specificity protein -- SP senile plaque -- TBI traumatic brain injury -- TH thyroid hormone -- TSS transcription start site -- VDAC voltage-dependent anion channel 1 -- VEGF vascular endothelial growth factor -- VEGFR2/Flk1 VEGF receptor tyrosine kinase; Pathology, Molecular -- Periodicals; Medicine -- Periodicals; Biochemistry -- Periodicals; Medicine -- Periodicals; Molecular Biology -- Periodicals; Pathologie moléculaire -- Périodiques; Médecine -- Périodiques; Electronic journals; 612.015
• DOI: 10.1016/j.mam.2016.10.004
• Languages: English
• ISSNs: 0098-2997

Abstract

Abstract: In 2000, the third member of the globin family was discovered in human and mouse brain and named neuroglobin (Ngb). Ngb is a monomeric 3/3 globin structurally similar to myoglobin and to the α- and β-chains of hemoglobin, however it displays a bis-histidyl six-coordinate heme-Fe atom. Therefore, ligand binding to the Ngb metal center is limited from the dissociation of the distal His(E7)64-Fe bond. From its discovery, more than 500 papers on Ngb structure, expression, reactivity, and localization have been published to highlight its biochemical properties and its role(s) in health and disease. In vivo experiments have shown that increased levels of Ngb significantly protect both heart and brain from hypoxic/ischemic and oxidative stress-related insults, whereas decreased Ngb levels lead to an exacerbation of tissue injuries. Although some contradictory data emerged, human Ngb overexpression has been hypothesized to protect neurons from mitochondrial dysfunctions and neurodegenerative disorders such as Alzheimer's disease, and to play a shielding role in cancer cells. Recently, the recognition of Ngb interactors and inducers enlarges the functions of this stress-inducible globin, opening new therapeutic approaches to prevent neuronal cell death. Here, structural and functional aspects of human Ngb are examined critically to highlight its roles in health and disease.