What happened when neuroglobin was increased in an Alzheimer’s mouse model?

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Neuroglobin (Ngb) is a vertebrate globin expressed primarily in neurons. It is induced by neuronal hypoxia and cerebral ischemia and protects against them.

To investigate the range and mechanism of Ngb’s neuroprotective action, researchers studied transgenic Ngb overexpression in mouse cortical neuron cultures in vitro and in Alzheimer’s disease (AD) transgenic APP(Sw,Ind) mice. They examined its effects on toxicity from NMDA and beta-amyloid (Abeta) in the cultures and on the AD mouse phenotype.

Compared with cortical neuron cultures from wild-type mice, cultures from Ngb-overexpressing transgenic mice (Ngb-Tg) were resistant to the toxic effects of NMDA and Abeta(25-35). This was measured using cell membrane lipid raft polarization, mitochondrial aggregation, lactate dehydrogenase release, and nuclear fragmentation.

Compared with APP(Sw,Ind) mice, double-transgenic Ngb-Tg x APP(Sw,Ind) mice had fewer thioflavin-S-stained extracellular Abeta deposits, lower levels of Abeta(1-40) and Abeta(1-42), and better behavioral performance in a Y-maze test of spontaneous alternations.

The findings suggest that Ngb’s neuroprotective action extends beyond hypoxic-ischemic insults. Ngb may protect neurons from NMDA and Abeta toxicity by inhibiting formation of a death-signaling membrane complex, and interventions that increase Ngb expression could potentially have therapeutic applications in AD and other neurodegenerative disorders.