Impaired hypoxic tolerance in APP23 mice: a dysregulation of neuroprotective globin levels

Although neuroglobin confers neuroprotection against Alzheimer's disease (AD) pathology, its expression becomes downregulated in late‐stage AD. Here, we provide evidence that indicates that this decrease is associated with the AD‐linked angiopathy. While wild‐type mice of different ages show upregulated cerebral neuroglobin expression upon whole‐body hypoxia, APP23 mice exhibit decreased cerebral transcription of neuroglobin. Interestingly, transcription of cytoglobin, whose involvement in amyloid pathology still needs to be elucidated, follows a similar pattern. To further unravel the underlying mechanism, we examined the expression levels of the RE‐1‐silencing transcription factor (REST/NRSF) after identifying a recognition site for it in the regulatory region of both globins. Neuroglobin‐cytoglobin‐REST/NRSF expression correlations are detected mainly in the cortex. This raises the possibility of REST/NRSF being an upstream regulator of these globins.