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Query: UMLS:C0022116 (
ischemia
)
91,303
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Globins are globular proteins for either transport or storage of oxygen which are critical for cellular metabolism. Four globins have been identified in rodent and human brains. Among them,
neuroglobin
, cytoglobin and hemoglobin chains are constitutively expressed in normal brain, while myoglobin is only expressed in some neurological disorders. Studies on the molecular structure, expression and functional features of these brain globins indicated that they may play crucial roles in maintenance of neural cell survival and activity, including neurons and astrocytes. Their regulation in neurological disorders may help thoroughly understand initiation and progression of
ischemia
, Alzheimer's disease and glioma,
etc
. Elucidation of the brain globin functions might remarkably improve medical strategies that sustain neurological homeostasis and treat neurological diseases. Here the expression pattern and functions of brain globins and their involvement in neurological disorders are reviewed.
...
PMID:Brain globins in physiology and pathology. 2786 83
Cerebral ischemia causes severe cell death or injury including axon breakdown or retraction in the brain. Axon regeneration is crucial for the functional recovery of injured neurons or brains after
ischemia
/reperfusion (I/R); however, this process has been proved extremely difficult in adult brains and there is still no effective therapy for it. Here we reported that
neuroglobin
(Ngb), a novel oxygen-binding or sensor protein existing predominantly in neurons or brains, functions as a driving factor for axon regeneration during I/R. Ngb was upregulated and accumulated in growth cones of ischemic neurons in primary cultures, rat, and human brains, correlating positively to the elevation of axon-regeneration markers GAP43, neurofilament-200, and Tau-1. Ngb overexpression promoted while Ngb knockdown suppressed axon regeneration as well as GAP43 expression in neurons during oxygen-glucose deprivation/reoxygenation (OGD/Re). By using specific pharmacological inhibitors, we identified p38 MAPK as the major downstream player of Ngb-induced axon regeneration during OGD/Re. Mechanistically, Ngb directly bound to and activated p38 in neurons upon OGD/Re. Serial truncation and point mutation of Ngb revealed that the 7-105 aa fragment of Ngb was required and the oxygen-binding site (His
64
) of Ngb was the major regulatory site for its p38 interaction/activation. Finally, administration of exogenous TAT-Ngb peptides significantly enhanced axon regeneration in cultured neurons upon OGD/Re. Taken together, Ngb promotes axon regeneration via O
2
-Ngb-p38-GAP43 signaling during I/R. This novel mechanism suggests potential therapeutic applications of Ngb for ischemic stroke and other related axonopathy.
...
PMID:Neuroglobin boosts axon regeneration during ischemic reperfusion via p38 binding and activation depending on oxygen signal. 2941 29
Background:
Obstructive sleep apnea (OSA) is a highly prevalent disease manifesting as intermittent hypoxia during sleep (IH) and is increasingly recognized as being independently associated with neurobehavioral deficits. These deficits may be due to increased apoptosis in the hippocampus and cerebral cortex, as well as increased oxidative stress and inflammation. It has been reported that
neuroglobin
(Ngb) is upregulated in response to hypoxia-
ischemia
insults and exhibits a protective role in
ischemia
-reperfusion brain injury. We hypothesized that transgenic overexpression of Ngb would attenuate spatial learning deficits in a murine model of OSA.
Methods:
Wild-type mice and Ngb overexpressing male mice (Ngb-TG) were randomly assigned to either IH or room air (RA) exposures. The effects of IH during the light period on performance in a water maze spatial task were assessed, as well as anxiety and depressive-like behaviors using elevated plus maze (EPM) and forced swim tests. Cortical tissues from all the mice were extracted for biochemical studies for lipid peroxidation.
Results:
Ngb TG mice exhibited increased Ngb immunoreactivity in brain tissues and IH did not elicit significant changes in Ngb expression in either Ngb-TG mice or WT mice. On a standard place training task in the water maze, Ngb-TG mice displayed preserved spatial learning, and were protected from the reduced spatial learning performances observed in WT mice exposed to IH. Furthermore, anxiety and depression levels were enhanced in WT mice exposed to IH as compared to RA controls, while alterations emerged in Ngb-TG mice exposed to IH. Furthermore, WT mice, but not Ngb-TG mice had significantly elevated levels of malondialdehyde in cortical lysates following IH exposures.
Conclusions:
In a murine model of OSA, oxidative stress responses and neurocognitive and behavioral impairments induced by IH during sleep are attenuated by the neuroprotective effects of Ngb.
...
PMID:Cognitive Deficits Are Attenuated in Neuroglobin Overexpressing Mice Exposed to a Model of Obstructive Sleep Apnea. 2992 22
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