Figure 3.

The impact of impaired Nrf2 pathway on glial large pore channels during MS. Under neuroinflammatory conditions, the increase in ROS triggers typically the activation of the Nrf2 transcription factor in glial cells (such as astrocytes and microglia), inducing the anti-inflammatory response element (ARE) pathway activation that finally restore the ROS levels. In these conditions, Nrf2 maintains an inhibitory tone on Cx43 hemichannels, keeping their activity in a physiological range. In contrast, during MS the proper function of the Nrf2 transcription factor is impaired, which result in decreased activation of ARE pathways accompanied of persistent and exacerbated opening of large pore channels, including Cx43 hemichannels and likely Panx1 channels in glial cells (see the main text). This figure was created in Biorender.