In conclusion, this study suggests TRH analog, Taltirelin possesses a protective effect on SH-SY5Y cells and rat primary midbrain neurons, as well as MPTP-induced subacute and rotenone-induced chronic PD mice models and this neuroprotective effect is associated with inhibition of apoptosis, ROS generation, phosphorylation of tau and α-synuclein, inhibition of AEP, thus providing evidence for applying a promising neuroprotective agent for treatment of PD. This evidence concerns the gene TRH and Parkinson disease.