Diagram of the hypothetical vicious cycle of glial activation signaling triggered in Parkinsonism during dopaminergic neuronal loss. (a) Dopaminergic neuronal death induces the release or leakage of ATP, which activates microglial cells through P2YR. (b) Activation of microglia induces the release of IFN-, which binds IFN-R in neighbor microglial and astroglial cells initiating the phosphorylation of STAT1. (c) Activation of astrocytes involves the release of TNF-, which may activate astrocytes through the activation of TNF-R by phosphorylating SAPK. (d) Importantly, released TNF- may also activate TNF-R present in dopaminergic neurons, which may induce new neuronal death.
