The Metabolomic Profile in Amyotrophic Lateral Sclerosis Changes According to the Progression of the Disease: An Exploratory Study
Carmen Marino,
Manuela Grimaldi,
Eduardo Maria Sommella,
Tania Ciaglia,
Angelo Santoro,
Michela Buonocore,
Emanuela Salviati,
Francesca Trojsi,
Arianna Polverino,
Pierpaolo Sorrentino,
Giuseppe Sorrentino,
Pietro Campiglia,
Anna Maria D’Ursi
Affiliations
Carmen Marino
PhD Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Manuela Grimaldi
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Eduardo Maria Sommella
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Tania Ciaglia
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Angelo Santoro
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Michela Buonocore
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Emanuela Salviati
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Francesca Trojsi
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Via Maggiore Salvatore Arena, Contrada San Benedetto, 81100 Caserta, Italy
Arianna Polverino
Institute of Diagnosis and Treatment Hermitage Capodimonte, Cupa delle Tozzole, 2, 80131 Naples, Italy
Pierpaolo Sorrentino
Institute of Applied Sciences and Intelligent Systems of National Research Council, Via Campi Flegrei 34, 80078 Pozzuoli, Italy
Giuseppe Sorrentino
Institute of Diagnosis and Treatment Hermitage Capodimonte, Cupa delle Tozzole, 2, 80131 Naples, Italy
Pietro Campiglia
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Anna Maria D’Ursi
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, 84084 Salerno, Italy
Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative pathology of the upper or lower motor neuron. Evaluation of ALS progression is based on clinical outcomes considering the impairment of body sites. ALS has been extensively investigated in the pathogenetic mechanisms and the clinical profile; however, no molecular biomarkers are used as diagnostic criteria to establish the ALS pathological staging. Using the source-reconstructed magnetoencephalography (MEG) approach, we demonstrated that global brain hyperconnectivity is associated with early and advanced clinical ALS stages. Using nuclear magnetic resonance (1H-NMR) and high resolution mass spectrometry (HRMS) spectroscopy, here we studied the metabolomic profile of ALS patients’ sera characterized by different stages of disease progression—namely early and advanced. Multivariate statistical analysis of the data integrated with the network analysis indicates that metabolites related to energy deficit, abnormal concentrations of neurotoxic metabolites and metabolites related to neurotransmitter production are pathognomonic of ALS in the advanced stage. Furthermore, analysis of the lipidomic profile indicates that advanced ALS patients report significant alteration of phosphocholine (PCs), lysophosphatidylcholine (LPCs), and sphingomyelin (SMs) metabolism, consistent with the exigency of lipid remodeling to repair advanced neuronal degeneration and inflammation.
