In summary, the present study demonstrated that a levodopa-induced increased in homocysteine has a detrimental effect on adult neurogenesis via NMDA receptor-mediated ERK signaling pathways, and modulation of levodopa-induced hyperhomocysteinemia by a NMDA antagonist or dopaminergic agonist is clinically relevant for human PD treatment in terms of adult neurogenesis. Here, MAPK1 is linked to hyperhomocysteinemia.