Although EP4 receptor is coupled to cAMP stimulation like EP2, the EP4-receptor pathway substantially works in a neuroprotective direction: in mouse in vivo model of PD, microglia-specific EP4 deficiency exacerbated microglial activation and T-cell infiltration in substantia nigra, and systemic administration of an EP4 agonist prevented a loss of dopaminergic neurons (Pradhan et al., 2017). This evidence concerns the gene PTGER4 and Parkinson disease.