Hong Bai,1 Wenhui Ma,2 Lei Zhu,1 Yaling Lu,3 Jiaojiao Fan,4 Mengjia Chen,1 Cong Huang2 

1Department of Neurology, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China; 2Department of Radiology, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China; 3Department of Health Management, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China; 4Department of Outpatient, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China

Correspondence: Cong Huang, Department of Radiology, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People’s Republic of China, Email magichc401@163.com

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.

Keywords: Parkinson’s disease, α-synuclein propagation, biomarkers, disease-modifying therapies, gene-environment interaction, mitochondrial dysfunction, deep brain stimulation, precision medicine