F4-neuroprostanes mediate neurological severity in Rett syndrome

Cinzia Signorini, Claudio De Felice, Silvia Leoncini, Anna Giardini, Maurizio D'Esposito, Stefania Filosa, Floriana Della Ragione, Marcello Rossi, Alessandra Pecorelli, Giuseppe Valacchi, Lucia Ciccoli, Joussef Hayek

Research output: Contribution to journalArticlepeer-review


Background: Rett syndrome (RTT) is a pervasive development disorder, mainly caused by mutations in the methyl-CpG binding protein 2 (MeCP2) gene. No reliable biochemical markers of the disease are available. Here we assess F4-neuroprostanes (F4-NeuroPs), lipid peroxidation products of the docosahexaenoic acid, as a novel disease marker in RTT and correlate it with clinical presentation, MeCP2 mutation type, and disease progression. In addition, we investigate on the impact of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on F4-NeuroPs levels. Methods: A case-control study design was used. A cohort of RTT patients (n=144) exhibiting different clinical presentations, disease stages, and MeCP2 gene mutations were evaluated. F4-NeuroPs were measured in free form using a GC/NICI-MS/MS technique. Plasma F4-NeuroPs levels in patients were compared to healthy controls and related to RTT forms, disease progression, and response to ω-3 PUFAs supplementation. Results: Plasma F4-NeuroPs levels were i) higher in RTT than in controls; ii) increased with the severity of neurological symptoms; iii) significantly elevated during the typical disease progression; iv) higher in MeCP2-nonsense as compared to missense mutation carriers; v) higher in typical RTT as compared to RTT variants; and vi) decreased in response to 12months ω-3 PUFAs oral supplementation. Conclusions: Quantification of plasma F4-NeuroPs provides a novel RTT marker, related to neurological symptoms severity, mutation type and clinical presentation.

Original languageEnglish
Pages (from-to)1399-1406
Number of pages8
JournalClinica Chimica Acta
Issue number15-16
Publication statusPublished - Jul 15 2011


  • ω-3 polyunsaturated fatty acids
  • Autism spectrum disorders
  • CDKL5
  • MeCP2
  • Neuroprostanes
  • Rett syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical
  • Medicine(all)


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