The contribution of the citrate pathway to oxidative stress in Down syndrome

Immunology. 2016 Dec;149(4):423-431. doi: 10.1111/imm.12659. Epub 2016 Oct 3.


Inflammatory conditions and oxidative stress have a crucial role in Down syndrome (DS). Emerging studies have also reported an altered lipid profile in the early stages of DS. Our previous works demonstrate that citrate pathway activation is required for oxygen radical production during inflammation. Here, we find up-regulation of the citrate pathway and down-regulation of carnitine/acylcarnitine carrier and carnitine palmitoyl-transferase 1 genes in cells from children with DS. Interestingly, when the citrate pathway is inhibited, we observe a reduction in oxygen radicals as well as in lipid peroxidation levels. Our preliminary findings provide evidence for a citrate pathway dysregulation, which could be related to some phenotypic traits of people with DS.

Keywords: ATP citrate lyase; Down syndrome; citrate pathway; inflammation; mitochondrial citrate carrier; oxidative stress.

MeSH terms

  • Anion Transport Proteins / genetics
  • Anion Transport Proteins / metabolism*
  • Carnitine / metabolism*
  • Carnitine Acyltransferases / genetics
  • Carnitine Acyltransferases / metabolism*
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism*
  • Cell Line, Transformed
  • Child, Preschool
  • Citric Acid / metabolism*
  • Down Syndrome / genetics
  • Down Syndrome / immunology
  • Down Syndrome / metabolism*
  • Gene Expression Regulation
  • Humans
  • Leukocytes / physiology*
  • Lipid Peroxidation
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Oxidative Stress
  • Phenotype
  • Quantitative Trait, Heritable


  • Anion Transport Proteins
  • Mitochondrial Proteins
  • Slc25a1 protein, human
  • Citric Acid
  • Carnitine Acyltransferases
  • Carnitine O-Palmitoyltransferase
  • Carnitine