Metabolomic and Proteomic Profiling of Serum-Derived Extracellular Vesicles from Early-Stage Amyotrophic Lateral Sclerosis Patients

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2025-02-15 DOI:10.1007/s12031-025-02315-w

Yara Al Ojaimi, Nicolas Vallet, Audrey Dangoumau, Débora Lanznaster, Clement Bruno, Antoine Lefevre, Samira Osman, Camille Dupuy, Patrick Emond, Patrick Vourc’h, Philippe Corcia, Zuzana Krupova, Charlotte Veyrat-Durebex, Hélène Blasco

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引用次数: 0

Abstract

The identification of reliable biomarkers for amyotrophic lateral sclerosis (ALS) is an unmet medical need for the development of diagnostic and therapeutic strategies. Brain-derived extracellular vesicles (EVs) have been described in peripheral blood serum and used as a direct readout of the status of the central nervous system. Here, we aimed to explore exosome-enriched EVs (referred to simply as EVs) from ALS patients via omics analysis at an early disease stage. Serum EVs were obtained from 9 healthy controls and 9 ALS patients. After EV purification, proteomic (LC‒MS/MS followed by TimsTOF Pro Mass Spectrometry) and metabolomic (Q Exactive mass spectrometer) analyses were performed. No differences in the size or concentration of EVs were observed between the controls and ALS patients. Proteomic analysis revealed 45 proteins differentially expressed in the EVs of ALS patients compared with those of controls. Metabolomic analysis revealed several distinctly represented metabolites involved in the citrate cycle and complex lipid metabolism between patients and controls. Interomics correlation analysis revealed 2 modules that were strongly associated with ALS and included several lipid metabolism-related proteins and metabolites. This study is the first to evaluate EVs by integrated proteomics and metabolomics in early-stage ALS patients, highlighting the technological progress in global inter-omics explorations of small biological samples. The differences observed in the levels of several exosomal proteins and metabolites, including phospholipids, could be used to identify serum biomarkers and novel players involved in ALS pathogenesis.

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.