Cholesterol metabolism is altered in Rett syndrome: a study on plasma and primary cultured fibroblasts derived from patients

PLoS One. 2014 Aug 12;9(8):e104834. doi: 10.1371/journal.pone.0104834. eCollection 2014.


Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Case-Control Studies
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Male
  • Methyl-CpG-Binding Protein 2 / deficiency
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Mice, Knockout
  • Mutation
  • Proprotein Convertase 9
  • Proprotein Convertases / blood
  • Receptors, LDL / metabolism
  • Rett Syndrome / blood
  • Rett Syndrome / genetics
  • Rett Syndrome / metabolism*
  • Scavenger Receptors, Class B / metabolism
  • Serine Endopeptidases / blood
  • Sterol Regulatory Element Binding Proteins / metabolism
  • Young Adult


  • MECP2 protein, human
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Receptors, LDL
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Sterol Regulatory Element Binding Proteins
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases

Grant support

The authors have no support or funding to report.