FIGURE 2.

Schematic illustration of the role of astroglial hemichannels in neurodegeneration in an AD mouse model (APP/PS1). In the hippocampus, Cx43 HCs are activated in astrocytes contacting Aβ plaques which are triggered by high [Ca²⁺]_i ①, while Panx1 hemichannels are only activated as a minor contributor triggered by proinflammatory cytokines ② (Yi et al., 2016). HC opening results in the influx of Ca²⁺ from extracellular to cytoplasm, allowing the high [Ca²⁺]_i maintenance ③ (Yi et al., 2016). HCs activation in astrocytes can lead to gliotransmitter release including glutamate and ATP ④, which then stimulate the intracellular neurotoxic cascades and resulting in neurodegeneration ⑤ (Yi et al., 2016). The astroglial connexin hemichannel blockers [such as Boldine (Yi et al., 2017) and TAT-Gap19 (Abudara et al., 2014)] may become new pharmaceutical tools that can alleviate the neuronal damage in AD ⑥. AD, Alzheimer’s disease; HC, hemichannel; ECM, extracellular matrix.