Neuroglobin, a Novel Target for Endogenous Neuroprotection against Stroke and Neurodegenerative Disorders

Abstract

Brain neurons and tissues respond to sublethal injury by activating endogenous protective pathways. Recently, following the failure of a large number of clinical trials for protective strategies against stroke that aim to inhibit a specific ischemia response pathway, endogenous neuroprotection has emerged as a more promising and hopeful strategy for development of therapeutics against stroke and neurodegenerative disorders. Neuroglobin (Ngb) is an oxygen-binding globin protein that is highly and specifically expressed in brain neurons. Accumulating evidence have clearly demonstrated that Ngb is an endogenous neuroprotective molecule against hypoxic/ischemic and oxidative stress-related insults in cultured neurons and animals, as well as neurodegenerative disorders such as Alzheimer’s disease, thus any pharmacological strategy that can up-regulate endogenous Ngb expression may lead to novel therapeutics against these brain disorders. In this review, we summarize recent studies about the biological function, regulation of gene expression, and neuroprotective mechanisms of Ngb. Furthermore, strategies for identification of chemical compounds that can up-regulate endogenous Ngb expression for neuroprotection against stroke and neurodegenerative disorders are discussed.

Chemical profiling and quantification of Gua-Lou-Gui-Zhi decoction by high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and ultra-performance liquid chromatography/triple quadrupole mass spectrometry

“…Galloyl glucoses such as pentagalloylglucose expresses multiple pharmaceutical including antioxidant, anti-inflammatory, cytoprotection and neuroprotective effect [45]. Phenolic acids offen showed good antioxidant activity, such as Cinnamic acid, a free radical scavenger, showed significant anti-inflammatory and anti-oxidation effects in a transient MCAO model, and also has been used as a phytochemical marker of Cinnamomi Ramulus [46]. Vanillic acid, a phenolic acids from Trichosanthis Radix, had antiplatelet aggregation effect that expressed potentials neuroprotective [47].…”

Alleviating Brain Stress: What Alternative Animal Models Have Revealed About Therapeutic Targets For Hypoxia and Anoxia

“…Ngb has potential roles as an oxygen storage protein or as an antioxidant, and increasing evidence suggests it could be an endogenous neuroprotective molecule against hypoxic/ischemic and oxidative stress-related insults in cultured neurons and animal models, as well as in neurodegenerative disorders such as Alzheimer’s disease [77]. …”

Neuroglobin overexpression improves sensorimotor outcomes in a mouse model of traumatic brain injury

“…Neuron survival is enhanced via an increased endogenous production of neuroglobin following hypoxia and ischemia [13]. Therefore, neuroglobin has been suggested to be neuroprotective in experimental models of stroke [17, 27] and in TBI [22, 28]. …”