Multiomics approach discloses lipids and metabolites profiles associated to Parkinson's disease stages and applied therapies

帕金森病 疾病 神经科学 医学 生物 病理
作者
Federica Carrillo,Nicole Piera Palomba,Marco Ghirimoldi,Camilla Didò,Giorgio Fortunato,Shahzaib Khoso,Tiziana Giloni,Marco Santilli,Tommaso Bocci,Alberto Priori,Sara Pietracupa,Nicola Modugno,E. Barberis,Marcello Manfredi,Paola Signorelli,Teresa Esposito
出处
期刊:Neurobiology of Disease [Elsevier]
卷期号:: 106698-106698
标识
DOI:10.1016/j.nbd.2024.106698
摘要

Profiling circulating lipids and metabolites in Parkinson's disease (PD) patients could be useful not only to highlight new pathways affected in PD condition but also to identify sensitive and effective biomarkers for early disease detection and potentially effective therapeutic interventions. In this study we adopted an untargeted omics approach in three group of patients (No L-Dopa, L-Dopa and DBS) to disclose whether long-term levodopa treatment with or without deep brain stimulation (DBS) could reflect a characteristic lipidomic and metabolomic signature at circulating level. Our findings disclosed a wide up regulation of the majority of differentially regulated lipid species that increase with disease progression and severity. We found a relevant modulation of triacylglycerols and acyl-carnitines, together with an altered profile in adiponectin and leptin, that can differentiate the DBS treated group from the others PD patients. We found a highly significant increase of exosyl ceramides (Hex2Cer) and sphingoid bases (SPB) in PD patients mainly in DBS group (p < 0.0001), which also resulted in a highly accurate diagnostic performance. At metabolomic level, we found a wide dysregulation of pathways involved in the biosynthesis and metabolism of several amino acids acids. The most interesting finding was the identification of a specific modulation of L-glutamic acid in the three groups of patients. L-glutamate levels increased slightly in No L-Dopa and highly in L-Dopa patients while decreased in DBS, suggesting that DBS therapy might have a beneficial effect on the glutamatergic cascade. All together, these data provide novel insights into the molecular and metabolic alterations underlying PD therapy and might be relevant for PD prediction, diagnosis and treatment.

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