In the present study, our findings demonstrated that the SHED-CM generated by our established and standardized procedures showed a prominent therapeutic efficacy that alleviated intracerebral CD4-positive cells, microglia activation, and α-synuclein accumulation, in brain areas (especially the substantial nigra and striatum), and concurrently improved the neurological deficits in a rotenone-induced PD rat model. This evidence concerns the gene CD4 and Parkinson disease.