Serotonergic Approaches in Parkinson’s Disease: Translational Perspectives, an Update

Parkinson’s disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of other neurotransmitters are affected by the disease process. One such neurotransmitter is serotonin (5-HT). 5-HT has been shown to play a role in several motor and nonmotor manifestations of PD, including tremor, cognition, depression and psychosis. 5-HT also seems to play a critical role in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. A breadth of preclinical studies and clinical trials have been conducted that aimed at modulating the 5-HT system in order to alleviate depression, cognitive deficits, psychosis, and dyskinesia. In this Review, we summarize recent advances in the 5-HT field in PD, but with a translational emphasis. We start by presenting a novel nonhuman primate model ...