title: Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions.
abstract: Metabolic phenotyping corresponds to the large-scale quantitative and qualitative analysis of the metabolome i.e., the low-molecular weight <1 KDa fraction in biological samples, and provides a key opportunity to advance neurosciences. Proton nuclear magnetic resonance and mass spectrometry are the main analytical platforms used for metabolic profiling, enabling detection and quantitation of a wide range of compounds of particular neuro-pharmacological and physiological relevance, including neurotransmitters, secondary messengers, structural lipids, as well as their precursors, intermediates and degradation products. Metabolic profiling is therefore particularly indicated for the study of central nervous system by probing metabolic and neurochemical profiles of the healthy or diseased brain, in preclinical models or in human samples. In this review, we introduce the analytical and statistical requirements for metabolic profiling. Then, we focus on key studies in the field of metabolic profiling applied to the characterization of animal models and human samples of central nervous system disorders. We highlight the potential of metabolic profiling for pharmacological and physiological evaluation, diagnosis and drug therapy monitoring of patients affected by brain disorders. Finally, we discuss the current challenges in the field, including the development of systems biology and pharmacology strategies improving our understanding of metabolic signatures and mechanisms of central nervous system diseases.
authors.affiliation: Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London, SW7 2AZ, UK.
authors.forename: Marc-Emmanuel
authors.initials: ME
authors.lastname: Dumas
authors.forename: Laetitia
authors.initials: L
authors.lastname: Davidovic
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D010641:Phenotype
chemical_list: D015415:Biomarkers