Abstract
Parkinson’s disease (PD) represents a progressive neurodegenerative disorder with escalating global burden, with mechanistic studies revealing α-synuclein propagation through gut-brain axis, mitochondrial defects, and neuroinflammatory cascades driven by genetic-environmental interplay. Recent advancements in diagnostic paradigms have successfully combined α-synuclein seed amplification assays with multimodal neuroimaging techniques, achieving an impressive diagnostic accuracy of 92% during the prodromal stages of disease. Phase II trials highlight disease-modifying potential of α-synuclein-targeting immunotherapies (40% reduction in motor decline) and LRRK2 kinase inhibitors showing blood-brain barrier penetration. Neuromodulation advances feature closed-loop deep brain stimulation systems with 63% superior symptom control versus conventional approaches. Current challenges center on biomarker validation across ethnic cohorts (30% variability in α-synuclein thresholds) and non-motor symptom management. Emerging solutions leverage single-cell spatial transcriptomics identifying dopaminergic neuron vulnerability signatures, coupled with wearable-enabled digital phenotyping achieving 89% prediction accuracy for motor fluctuations. This synthesis underscores the critical transition from symptomatic care to precision-targeted interventions of PD pathogenesis.