A globin for the brain.
The discovery that a myoglobin-like hemeprotein (called neuroglobin) is expressed in our brain raised considerable curiosity from the standpoints of biochemistry and pathophysiology alike. Neuroglobin is involved in neuroprotection from damage due to hypoxia or ischemia in vitro and in vivo; overexpression of neuroglobin ameliorates the recovery from stroke in experimental animals. The mechanism underlying this remarkable effect is still mysterious. Structural studies revealed that neuroglobin has a typical globin fold, and despite being hexacoordinated, it binds reversibly O2, CO, and NO, undergoing a substantial conformational change of the heme and of the protein. The possible mechanisms involved in neuroprotection are briefly reviewed. Neuroglobin is unlikely to be involved in O2 transport (like myoglobin), although it seems to act as a sensor of the O2/NO ratio in the cell, possibly regulating the GDP/GTP exchange rate forming a specific complex with the G(alpha beta gamma)-protein when oxidized but not when bound to a gaseous ligand. Thus it appears that neuroglobin is a stress-responsive sensor for signal transduction in the brain, mediated by a ligand-linked conformational change of the protein.
Brunori
M
M
Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Biochemical Sciences, University of Rome La Sapienza, Rome, Italy. maurizio.brunori@uniroma1.it
Vallone
B
B
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000502:physiology*; D005914:Globins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology; D000078787:Neuroglobin; D009474:Neurons / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
D008024:Ligands; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D010100:Oxygen