CHSU Discovery

Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of
dopaminergic neurons in the substantia nigra, leading to motor and nonmotor symptoms. The
pathophysiology of PD involves a complex interplay of genetic, environmental, and biochemical factors,
including the accumulation of alpha-synuclein protein aggregates, mitochondrial dysfunction, oxidative
stress, and neuroinflammation. Current pharmacological treatments primarily focus on alleviating
symptoms, with levodopa (LD) being the gold standard for motor symptom management. Additionally,
DOPA decarboxylase (DDC) enzyme inhibitors, dopamine agonists (DA), monoamine oxidase B (MAO-B)
inhibitors, catechol-O-methyl transferase (COMT) inhibitors, and centrally acting anticholinergics are
employed to modulate dopaminergic/cholinergic signaling and improve quality of life. Despite these
advances, the long-term efficacy of existing therapies diminishes over time and presents with severe adverse
effects, necessitating the exploration of novel therapeutic approaches. Future drug treatments should aim to
address disease progression through neuroprotective strategies, such as gene therapy, immunotherapy
targeting alpha-synuclein, and neurorestorative approaches that promote neurogenesis and synaptic
plasticity. There are some limitations to consider with these novel therapies, such as current preclinical or
early clinical phases with small sample sizes and follow-up trials. This narrative review aims to provide
insight into the existing and emerging pharmacological treatment options for the management of PD, while
highlighting the need for innovative strategies to improve outcomes for individuals living with PD,
comparing the benefits versus risks.