Neuroglobin Expression Models as a Tool to Study Its Function

Figure 1

Overview of the potential Ngb neuroprotective mechanisms in neurons. The schematic presentation is a magnification of the boxed area in a neuron. Ngb is detected to detoxify harmful excesses of NO and to scavenge ROS and RNS amongst others by its association witch Cyt c₁. Mitochondrial translocation suggested by the latter is exerted by HTT. Ngb has a guanosine nucleotide dissociation inhibitor (GDI) activity and can prevent Gα from binding to the Gβγ complex, which promotes neuronal survival. Ngb also may inhibit the dissociation of RAC-1 from its endogenous GDI, preventing actin polymerisation and microdomain aggregation. Furthermore, Ngb might inhibit opening of mPTP pores of mitochondria and subsequent Cyt c (Fe³⁺) release. Ngb also converts apoptotic Cyt c (Fe³⁺) to Cyt c (Fe²⁺). Furthermore, Ngb might modulate the AKT/IP3 signalling pathway and associate with Na⁺/K⁺ ATPase in order to promote neuroprotection. Lastly, while Ngb is able to bind oxygen, its oxygen affinity value only attains 7.5 Torr. Given this value to be lower than the O₂ tension within neurons, it is unlikely that Ngb exerts a respiratory function under basal conditions. Potentially harmful species are indicated in dark pink and converted nonharmful species in light pink. Ngb: neuroglobin; ROS: reactive oxygen species; RNS: reactive nitrogen species; ETC: electron transport chain; GDI: guanosine nucleotide dissociation inhibitor; Cyt c: cytochrome c; mPTP: mitochondrial permeability transition pore; GDP: guanosine diphosphate; RAC-1: ras-related C3 botulinum toxin substrate 1; Cyt c₁: cytochrome c₁; HTT: huntingtin; VDAC: voltage-dependent anion channel 1; IP3: inositol triphosphate; PIP3: phosphatidylinositol (3,4,5)-trisphosphate.