代谢组学分析揭示帕金森病的诊断生物标志物和失调通路。
Metabolomic profiling uncovers diagnostic biomarkers and dysregulated pathways in Parkinson's disease.
作者信息
Chen Hongfang, Cheng Xing, Pan Xiaoling, Yao Yu, Chen Lin, Fu Yaming, Pan Xinran
机构信息
Department of Neurology, The Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
出版信息
Front Neurol. 2025 Jun 4;16:1608031. doi: 10.3389/fneur.2025.1608031. eCollection 2025.
BACKGROUND
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and it has an unclear pathogenesis and lacks validated, specific biomarker-based diagnostic approaches, particularly in PD patients with rapid eye movement (REM) sleep behavior disorder (PD-RBD).
METHODS
Using untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, serum profiles of 41 drug-naïve PD patients [including 19 PD-RBD and 22 PD without RBD (PD-nRBD) patients] and 20 healthy controls (HCs) were analyzed.
RESULTS
Comparative analyses revealed 144 dysregulated metabolites in PD patients versus HCs, with 7 metabolites-sodium deoxycholate, S-adenosylmethionine, L-tyrosine, 3-methyl-L-tyrosine, 4,5-dihydroorotic acid, (6Z)-octadecenoic acid, and allantoin-demonstrating high classification accuracy [area under the curve (AUC) > 0.93]. Compared with PD-nPBD patients, PD-RBD patients exhibited distinct metabolic profiles, characterized by 21 differentially expressed metabolites, including suberic acid, 3-methyl-L-tyrosine, and methyl (indol-3-yl) acetate (AUC > 0.86). Notably, 3-methyl-L-tyrosine displayed dual dynamics, reflecting dopaminergic depletion in PD and compensatory metabolic adaptations in PD-RBD. Pathway enrichment analysis implicated central carbon metabolism (CCM) disruption in PD and peroxisome proliferator-activated receptor (PPAR) signaling pathway inactivation in PD-RBD.
CONCLUSION
These findings reveal potential serum-based biomarkers for PD and PD-RBD, highlight CCM and PPAR pathways as therapeutic targets, and underscore the role of metabolic dysregulation in PD pathophysiology.
背景
帕金森病（PD）是第二常见的神经退行性疾病，其发病机制尚不清楚，缺乏基于经过验证的特异性生物标志物的诊断方法，尤其是在伴有快速眼动（REM）睡眠行为障碍的PD患者（PD-RBD）中。
方法
采用非靶向液相色谱-质谱（LC-MS）代谢组学方法，分析了41例未用药的PD患者[包括19例PD-RBD患者和22例无RBD的PD（PD-nRBD）患者]以及20名健康对照（HCs）的血清谱。
结果
比较分析发现，与HCs相比，PD患者中有144种代谢物失调，其中7种代谢物——脱氧胆酸钠、S-腺苷甲硫氨酸、L-酪氨酸、3-甲基-L-酪氨酸、4,5-二氢乳清酸、（6Z）-十八碳烯酸和尿囊素——显示出较高的分类准确性[曲线下面积（AUC）>0.93]。与PD-nPBD患者相比，PD-RBD患者表现出独特的代谢谱，其特征为21种差异表达的代谢物，包括辛二酸、3-甲基-L-酪氨酸和乙酸（吲哚-3-基）甲酯（AUC>0.86）。值得注意的是，3-甲基-L-酪氨酸呈现双重动态变化，反映了PD中多巴胺能的耗竭以及PD-RBD中的代偿性代谢适应。通路富集分析表明，PD中存在中心碳代谢（CCM）紊乱，而PD-RBD中过氧化物酶体增殖物激活受体（PPAR）信号通路失活。
结论
这些发现揭示了PD和PD-RBD潜在的基于血清的生物标志物，突出了CCM和PPAR通路作为治疗靶点的作用，并强调了代谢失调在PD病理生理学中的作用。
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