Neuroglobin increases brain fitness Commentary to: 'Neuroglobin overexpression improves sensorimotor outcomes in a mouse model of traumatic brain injury'

摘要

Mammalian brains are exquisitely sensitive to low oxygen levels and respond to hypoxia with a variety of protective mechanisms that increase anaerobic metabolism and oxygen delivery. This allows the brain to function with high energy efficiency and minimizes the pathological effects of deficient energy supplies. Neuroglobin and cytoglobin are recently discovered respiratory proteins that binds to oxygen reversibly and thus could act as neuronal 'myoglobins' which are critical for oxygen supply to the mitochondria during exercise. Both, neuroglobin and cytoglobin are structurally similar to myoglobin and their oxygen binding affinities resemble that of myoglobin. Neuroglobin is confined mainly to brain and retina, whereas, cytoglobin is present in various tissues including brain [10]. Interestingly, the expression of Ngb is 100 times higher in retina than in brain. Ngb has been implicated in offering protection in neurological conditions that involve hypoxic-ischemic insult [8]. The potential mechanisms of the neu-roprotection by Ngb involve scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS) [2]. In addition, Ngb promotes neuronal survival by binding to cytosolic cytochrome c thus preventing activation of intrinsic apoptotic pathway [6]. Using yeast two hybrid system Ngb-interacting proteins were identified include those involved in energy metabolism, mitochondrial function, and signaling pathways for cell survival and proliferation [20]. Some of the functions regulated by Ngb are shown in Fig. 1. Ngb has been upregulated in many neurological conditions that include stroke, epilepsy, Alzheimer's disease, whereas, Ngb expression declines in aging and following sleep deprivation [15-17].