The Role of the Serotonergic System of the Brain in the Pathogenesis of Parkinson’s Disease

The traditional view of Parkinson’s disease (PD) relies on dopamine depletion in the striatum. However, PD is a multi-systemic disease that affects extra-dopaminergic systems. One of these is the serotonergic (5-HT) system, which has been widely investigated in PD. Although the 5-HT system has one transporter (SERT) and 14 receptor subtypes, most research in PD has concentrated on SERT and serotonergic type 1A and 2A receptors (5-HT1A and 5-HT2A). Degeneration of neurons causes a drop in serotonin levels, resulting in serotonergic system malfunction, which causes persistent fatigue, depression, and sleep difficulties. Several other activities of the serotonergic system have been linked to it, including cognition, emotion, and motor behavior; hence, disrupted serotonergic neurotransmission contributes to the motor and non-motor aspects often associated with PD. The goals of this article are to summarise and evaluate the studies that have explored the serotonergic system in PD and compare animal models, recapitulate existing knowledge, and identify areas that require more study and understanding.