Current and emerging drugs for Parkinson's disease: mechanisms, clinical evidence, and future directions

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and α-synuclein pathology, resulting in disabling motor and non-motor symptoms. Pharmacotherapy remains the cornerstone of PD management, yet current treatments are largely symptomatic and fail to halt disease progression. In recent years, substantial advances have been made in both dopaminergic and non-dopaminergic therapeutic strategies. Novel formulations of levodopa and dopamine agonists aim to provide more stable dopaminergic stimulation and reduce motor fluctuations. Meanwhile, emerging non-dopaminergic agents targeting glutamatergic, serotonergic, adenosinergic, and cholinergic systems offer new options for managing dyskinesia, gait impairment, and neuropsychiatric symptoms. Importantly, growing efforts are directed toward disease-modifying therapies, including α-synuclein immunotherapy, inhibitors of protein misfolding and aggregation, glucocerebrosidase-targeted interventions, and neuroprotective agents that modulate mitochondrial dysfunction, oxidative stress, inflammation, and metabolic signaling. Although many candidates have shown encouraging preclinical or early clinical results, definitive disease-modifying efficacy remains to be established. This review summarizes recent progress in PD pharmacotherapy, highlights translational challenges, and discusses future directions toward precision medicine and combination strategies for achieving sustained symptomatic control and disease modification.