Fig. 9: The graphical abstract shows the unique characteristics of neuron damage in the SN of PD mice due to oligodendrocyte and astrocyte crosstalk.

In the PD environment, the interaction between FGF1 secreted by oligodendrocytes and FGF9 in the SN with FGFR1, FGFR2, and FGFR3 receptors on astrocytes is weakened, which may reduce their ability to protect neurons from oxidative damage. Therefore, ferroptosis in the midbrain SN primarily occurs in astrocytes under the dysregulation of oligodendrocytes, subsequently leading to neuronal ferroptosis. The significant accumulation of ROS released by astrocytes and oligodendrocytes, the substantial buildup of iron ions in the SN, and the marked reduction of antioxidant factors NRF2/SLC7A11/GPX4 may be specific pathways leading to the substantial decrease in SN dopaminergic neurons.