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Publications

Journal Article Epublish

PubMed: 40534749 DOI: 10.3389/fneur.2025.1608031

Metabolomic profiling uncovers diagnostic biomarkers and dysregulated pathways in Parkinson's disease.

Front Neurol 16:1608031

Authors: Hongfang Chen, Xing Cheng, Xiaoling Pan, Yu Yao, Lin Chen, Yaming Fu, Xinran Pan

Affiliations

  • Department of Neurology, The Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
  • 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.
  • Central Laboratory, The Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.

Abstract

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.

MeSH

Serum, Parkinson Disease, Biomarkers, Metabolomics, Tyrosine, Peroxisome Proliferator-Activated Receptors