Figure 1.

A schematic figure for the involvement of glial TRPM2 channel in plasticity of CNS and AD. We proposed that the activation of TRPM2 channels in microglia and astrocytes produces Ca²⁺ overload and subsequent inflammation and oxidative stress which results in mitochondrial dysfunctions, [Ca²⁺]_i increase, Aβ accumulation in neurons, PSD95 reduction, glutamate receptor dysfunction, and finally change of plasticity and dementia. On the other hand, extinct factors such as aging and diabetes can result in increase of extracellular Aβ, which activates the above pathways. The third pathway may be that activation of neuronal TRPM2 channel enhances [Ca²⁺]_i and phosphorylates GSK3β and subsequent pathway to change plasticity.