Metabolomics: A Tool to Understand the Impact of Genetic Mutations in Amyotrophic Lateral Sclerosis

Genes (Basel). 2020 May 11;11(5):537. doi: 10.3390/genes11050537.


Metabolomics studies performed in patients with amyotrophic lateral sclerosis (ALS) reveal a set of distinct metabolites that can shed light on the pathological alterations taking place in each individual. Metabolites levels are influenced by disease status, and genetics play an important role both in familial and sporadic ALS cases. Metabolomics analysis helps to unravel the differential impact of the most common ALS-linked genetic mutations (as C9ORF72, SOD1, TARDBP, and FUS) in specific signaling pathways. Further, studies performed in genetic models of ALS reinforce the role of TDP-43 pathology in the vast majority of ALS cases. Studies performed in differentiated cells from ALS-iPSC (induced Pluripotent Stem Cells) reveal alterations in the cell metabolism that are also found in ALS models and ultimately in ALS patients. The development of metabolomics approaches in iPSC derived from ALS patients allow addressing and ultimately understanding the pathological mechanisms taking place in any patient. Lately, the creation of a "patient in a dish" will help to identify patients that may benefit from specific treatments and allow the implementation of personalized medicine.

Keywords: ALS; genetics; iPSC; metabolomics; personalized medicine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Animals
  • C9orf72 Protein / genetics
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Genome-Wide Association Study
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology
  • Metabolomics*
  • Mutation*
  • Precision Medicine
  • RNA-Binding Protein FUS / genetics
  • Superoxide Dismutase-1 / genetics


  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • FUS protein, human
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • TARDBP protein, human
  • Superoxide Dismutase-1