Dysregulation of serotonergic neurotransmission in Parkinson disease: A key duet

Parkinson's disease (PD) is the most common movement disorder, affecting approximately 1% of the general population over 65 years of age. PD is commonly associated with the development of motor and non-motor symptoms. Non-motor symptoms arise decades earlier than motor symptoms due to the degeneration of GABAergic, serotonergic, and other neurons involved in autonomic regulation. However, motor symptoms in PD are developed due to degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc) of midbrain. The PD neuropathology is related to the progressive loss of the dopaminergic neurons in the SNpc of midbrain. Particularly, dysfunction of serotonergic system is implicated in the development of non-motor symptoms such as sleep disorders, cognitive dysfunction, depression and anxiety. In addition, dysfunction of serotonergic neurons which affects the dopaminergic neurons in the SNpc leads to the development of motor symptoms. Moreover, dysfunction of serotonergic neurons is associated with the development of L-dopamine (L-DOPA)-induced dyskinesia. Consistently, administration of serotonin (5-HT) receptor agonist attenuates the development of L-DOPA-induced dyskinesia. These findings emphasized the possible role of serotonergic system in PD. However, the underlying mechanisms that mediate the latent effect of 5-HT in PD are not completely elucidated. Therefore, this mini-review aims to discuss the exact role of 5-HT in PD, and how the 5-HT modulators affect PD neuropathology.