Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging.

Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species Amyloid β (Aβ) plays a crucial role in Alzheimer's disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived in mediating microglial response to Aβ peptide 1-42 (Aβ₄₂) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ₄₂ markedly induced BV2 cell duanyu1670 production, Nox2 expression, p47^phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3-4 months) controls, midbrain tissues from wild-type aging mice (20-22 months) had significantly higher levels of Nox2-derived duanyu1670 production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25-38 years) and old age (61-85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ₄₂ stimulation and in aging-associated microgliosis and brain inflammation.

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