Bai Hong, Ma Wenhui, Zhu Lei, Lu Yaling, Fan Jiaojiao, Chen Mengjia, Huang Cong
Department of Neurology, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People's Republic of China.
Department of Radiology, No. 926 Hospital, Joint Logistics Support Force of PLA, Kaiyuan, Yunnan, 661699, People's Republic of China.
Neuropsychiatr Dis Treat. 2025 Sep 4;21:1945-1953. doi: 10.2147/NDT.S540718. eCollection 2025.
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.
帕金森病（PD）是一种进行性神经退行性疾病，全球负担不断加重。机制研究表明，α-突触核蛋白通过肠-脑轴传播、线粒体缺陷以及由基因-环境相互作用驱动的神经炎症级联反应。诊断模式的最新进展已成功将α-突触核蛋白种子扩增检测与多模态神经成像技术相结合，在疾病前驱期实现了高达92%的惊人诊断准确率。II期试验突出了靶向α-突触核蛋白免疫疗法（运动功能衰退降低40%）和显示出可穿透血脑屏障的LRRK2激酶抑制剂的疾病修饰潜力。神经调节方面的进展包括闭环深部脑刺激系统，与传统方法相比，其症状控制效果提高了63%。当前的挑战集中在不同种族人群生物标志物的验证（α-突触核蛋白阈值存在30%的变异性）以及非运动症状的管理。新兴解决方案利用单细胞空间转录组学识别多巴胺能神经元易损特征，并结合可穿戴设备实现的数字表型分析，对运动波动的预测准确率达到89%。这一综述强调了从对症治疗向针对PD发病机制的精准靶向干预的关键转变。
