Current Perspectives on Pathogenesis, Clinical Manifestations, and Treatment of Parkinson's Disease

Parkinson's disease (PD) represents a progressive neurodegenerative disorder characterized by both motor and non-motor manifestations. The condition emerges through complex interactions between genetic susceptibility and environmental triggers, leading to the characteristic loss of dopaminergic neurons in the substantia nigra pars compacta. During the prodromal phase, patients often experience non-motor symptoms including rapid eye movement sleep disorder, anosmia, constipation, and depression. As the disease advances, motor symptoms become apparent, manifesting as tremor, rigidity, bradykinesia, and postural instability. The underlying molecular mechanisms involve α-synuclein aggregation, mitochondrial dysfunction, impaired protein clearance systems, neuroinflammation, and oxidative stress. Multiple neurotransmitter systems beyond dopamine, including noradrenergic, glutamatergic, serotonergic, and adenosine pathways, contribute to the diverse clinical presentation. Diagnosis remains primarily clinical, supported by neuroimaging and specific biomarker tests to differentiate PD from other parkinsonian syndromes. Current therapeutic strategies focus on symptom management through pharmacological interventions, particularly dopamine replacement therapy, along with surgical options like deep brain stimulation for advanced cases. While existing treatments effectively manage motor symptoms, they do not alter disease progression.