Existing and Emerging Metabolomic Tools for ALS Research

Abstract

Growing evidence suggests that aberrant energy metabolism could play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Despite this, studies applying advanced technologies to investigate energy metabolism in ALS remain scarce. The rapidly growing field of metabolomics offers exciting new possibilities for ALS research. Here, we review existing and emerging metabolomic tools that could be used to further investigate the role of metabolism in ALS. A better understanding of the metabolic state of motor neurons and their surrounding cells could hopefully result in novel therapeutic strategies.

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

“…The quantification of the metabolites differs remarkably from the techniques and strategies used. Relative and absolute quantification are complementary techniques for metabolic discovery and validation and can be attained by untarget and target strategies [ 15 ]. In addition, to achieve an efficient quantification of specific metabolites in metabolomic studies, high-throughput tools are needed [ 15 , 16 ].…”

“…These are the most common strategies used in metabolomics to specific measure metabolites in a sample; however, they do not give a general idea of the metabolic flux in the biological condition analyzed. For more dynamic analysis, it is possible to combine MS or NMR with stable isotope tracing to predict the metabolic networks and pathways and, consequently, indirectly evaluate the biological effect of the metabolic changes found [ 15 , 30 , 31 , 32 ].…”

“…With the recent implementation of single-cell and in vivo real-time studies, the need for more sensitive and dynamic ways of identifying and quantifying small quantities of metabolites has emerged. Thus, recent studies have evaluated the tissue metabolomics in vivo through stable isotope tracers to delimitate the systemic metabolite kinetics, physiological function, and mechanisms affected by genetic variants or metabolites of interest [ 15 , 33 , 34 , 35 , 36 ]. These techniques can be followed by the traditional metabolomic analysis with MS or NMR to measure metabolic profile [ 15 ].…”

“…Single-cell analysis has grown in the past few years due to its high specificity and ability to analyze different cell types separately [ 15 ]. However, cell separation and metabolite quantification are still problematic, requiring the development of new technologies, such as microfluid arrays and nanodevices for cell separation [ 37 , 38 , 39 ].…”

“…Moreover, new analytical methods have been developed for single-cell metabolomic and lipidomic quantification, such as matrix-assisted laser desorption ionization (MALDI), live single-cell mass spectrometry (LSC-MS), and secondary ionization mass spectrometry (SIMS) [ 40 , 41 , 42 , 43 , 44 ]. These have higher sensitivity and resolution to detect a small concentration of metabolites and are commonly associated with a subsequent MS analysis [ 15 ]. Furthermore, more sensitive metabolite quantification methods are also attractive to discriminate between different isomers, thus increasing accuracy in biomarker identification.…”