Circulating Metabolites as Potential Biomarkers for Neurological Disorders-Metabolites in Neurological Disorders

Abstract

There are, still, limitations to predicting the occurrence and prognosis of neurological disorders. Biomarkers are molecules that can change in different conditions, a feature that makes them potential tools to improve the diagnosis of disease, establish a prognosis, and monitor treatments. Metabolites can be used as biomarkers, and are small molecules derived from the metabolic process found in different biological media, such as tissue samples, cells, or biofluids. They can be identified using various strategies, targeted or untargeted experiments, and by different techniques, such as high-performance liquid chromatography, mass spectrometry, or nuclear magnetic resonance. In this review, we aim to discuss the current knowledge about metabolites as biomarkers for neurological disorders. We will present recent developments that show the need and the feasibility of identifying such biomarkers in different neurological disorders, as well as discuss relevant research findings in the field of metabolomics that are helping to unravel the mechanisms underlying neurological disorders. Although several relevant results have been reported in metabolomic studies in patients with neurological diseases, there is still a long way to go for the clinical use of metabolites as potential biomarkers in these disorders, and more research in the field is needed.

Keywords: Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; epilepsy; magnetic nuclear resonance; mass spectrometry; metabolomics; multiple sclerosis; stroke.

Figure 1

Circulating metabolites. Metabolites are small molecules that act locally, in the tissue where they are produced, or systemically, when released to the extracellular environment. In the latter case, metabolites can circulate and be identified in different biofluids, such as plasma serum, urine, and cerebral spinal fluid. Circulating metabolites can be released as free molecules or inside vesicles. The production of metabolites can be influenced by changes in the external or internal environment, such as the microbiome, as well as by the occurrence of disease. In this last case, the disease processes may impact metabolite production and, thus, make it possible to use metabolites as disease biomarkers. The figure was created with Biorender.com.

Figure 2

Metabolomic scheme for identifying biomarkers. Circulating metabolites are found in biofluids and may be used as disease biomarkers. Metabolomics can be applied to identify metabolites using high-throughput techniques, such as mass spectrometry or nuclear magnetic resonance (NMR). By processing and analyzing the data from metabolomics studies, one can identify specific metabolites as disease biomarkers. This figure was created with Biorender.com.