Rett syndrome (RTT) is a relatively rare form of autism, affecting almost exclusively females, which is caused in the overwhelming majority of cases by the X-linked methyl-CpG binding protein 2 gene (MeCP2) gene and for which no definitive cure exists to date. RTT can be considered a very interesting natural model of autism spectrum disorder, ultimately ending up in a neuronal disease, with reduced brain size, smaller neuronal soma, presynaptic abnormalities, and postsynaptic morphological defects resulting in an overall decrease in synapse number and creating an abnormal excitatory/inhibitory balance. Ongoing investigations by our group have pointed out a previously unrecognized role of oxidative imbalance in the pathogenesis of this condition characterized by wide phenotypic variability. Here, we explore the potential value as biomarkers for a series of F2-IsoP-like molecules, termed F4-neuroprostanes (F4-NeuroPs) and representing the oxidation end-products from docosahexaenoic acid (DHA C22:6 ω-3), an essential constituent of the nervous tissue which is particularly enriched in neuronal membranes. Our investigations, performed in a large RTT patients cohort, indicate that plasma F4-NeuroPs concentrations are proportional to phenotype severity and type of MeCP2 mutation. These data underline the unrecognized role of oxidative damage in the pathogenesis of this genetic model of autism, and indicate the potential value of plasma F4-NeuroPs as a potential biomarker helpful in screening the disease.
NEUROPROSTANES AND NEUROLOGICAL SEVERITY IN RETT SYNDROME
VALACCHI, Giuseppe;
In corso di stampa
Abstract
Rett syndrome (RTT) is a relatively rare form of autism, affecting almost exclusively females, which is caused in the overwhelming majority of cases by the X-linked methyl-CpG binding protein 2 gene (MeCP2) gene and for which no definitive cure exists to date. RTT can be considered a very interesting natural model of autism spectrum disorder, ultimately ending up in a neuronal disease, with reduced brain size, smaller neuronal soma, presynaptic abnormalities, and postsynaptic morphological defects resulting in an overall decrease in synapse number and creating an abnormal excitatory/inhibitory balance. Ongoing investigations by our group have pointed out a previously unrecognized role of oxidative imbalance in the pathogenesis of this condition characterized by wide phenotypic variability. Here, we explore the potential value as biomarkers for a series of F2-IsoP-like molecules, termed F4-neuroprostanes (F4-NeuroPs) and representing the oxidation end-products from docosahexaenoic acid (DHA C22:6 ω-3), an essential constituent of the nervous tissue which is particularly enriched in neuronal membranes. Our investigations, performed in a large RTT patients cohort, indicate that plasma F4-NeuroPs concentrations are proportional to phenotype severity and type of MeCP2 mutation. These data underline the unrecognized role of oxidative damage in the pathogenesis of this genetic model of autism, and indicate the potential value of plasma F4-NeuroPs as a potential biomarker helpful in screening the disease.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
