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Metabolomics in Neurological Diseases

Metabolomics in Neurological Diseases

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Metabolomics seeks associations between metabolites and physiological or pathological changes by quantitatively or qualitatively analyzing all small molecule metabolites in an organism with molecular weights between 100 and 1000 Da. Untargeted metabolomics and targeted metabolomics are the two component aspects of metabolomics. Untargeted metabolomics aims to obtain as many metabolites as possible by unbiased analysis of the entire metabolome. Targeted metabolomics uses targeted metabolite standards to establish optimized analytical methods and standard curves, and then analyzes samples to accurately quantify specific metabolites. The main analytical platforms commonly used in metabolomics are nuclear magnetic resonance (NMR) and mass spectrometry (MS).

Metabolomics in Neurological DiseasesFig 1. Analytical workflow of metabolomics studies (Shao et al., 2019).

Biomarkers can be used for the diagnosis of disease, to discern the stage and progression of disease, or for the assessment of disease risk and prognosis. Many diseases undergo specific changes in the chemical and biochemical characteristics of biological fluids before the appearance of clinical symptoms. These changes may become potential biomarkers for early diagnosis of diseases.

Metabolomic techniques are increasingly used in the study of central neurological diseases, such as Alzheimer's-disease (AD), depression, and Parkinson's disease (PD). There is a lack of early biomarkers to diagnose CNS disorders. Because of their insidious onset, central neurological diseases are often overlooked at their early onset, resulting in poor follow-up and prognosis. Metabolomics techniques can be used to analyze biofluids such as cerebrospinal fluid (CSF), plasma, urine, and stool to explore biomarkers for early diagnosis of CNS disorders.

Metabolomics in Neurological DiseasesFig 2. Overview of the metabolic pathway dysregulations in PD (Shao et al., 2019).

The occurrence of neurological diseases is associated with disorders of neurotransmitters, phospholipids, steroids and other metabolism and abnormal mitochondrial function. Neurotransmitters in the brain are generally composed of small molecules such as dopamine (DA), epinephrine (EP), norepinephrine (NE), 5-hydroxytryptamine (5-HT), histamine, acetylcholine (Ach), y-aminobutyric acid (GABA), and glutamate (Glu).

These neurotransmitters can interact with each other in terms of their release or reuptake while transmitting signals. Therefore, disruption of any of these metabolic pathways may lead to the development of CNS disorders. Metabolomics techniques, which can accurately quantify these small molecules and their metabolites simultaneously and monitor multiple metabolic pathways simultaneously, are increasingly showing irreplaceable advantages in CNS research.

In addition, to distinguish the metabolic changes caused by drug treatment factors and disease factors, metabolomics techniques can be used to study healthy individuals, first-episode patients and post-treatment patients separately, so as to reveal the pathological processes of CNS diseases, find valuable biomarkers, identify disease subtypes, evaluate drug efficacy and side effects, and search for new targets of action for new drug development.

Reference

  1. Shao, Y., & Le, W. (2019). Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease. Molecular neurodegeneration, 14(1), 1-12.

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