title: OxInflammation in Rett syndrome.
abstract: Rett syndrome (RTT) is an orphan progressive neurodevelopmental disease affecting almost exclusively females (frequency 1:10,000). RTT clinical expression is typically characterized by loss of purposeful hand movements, severe mental retardation and motor impairment, breathing disorders, ataxia and increased risk of sudden death. Although the main genetic cause, i.e. mutation in the methyl-CpG binding protein 2 gene (MECP2), has been already identified, the molecular and pathogenic mechanisms by which MECP2 deficiency drives pathology in RTT remains not fully understood. A wealth of evidence from our and other laboratories suggests a potential causal relationship between MECP2 dysfunction and systemic redox imbalance, a condition that has been widely found in association with RTT. In turn, a "short-circuit" of redox pathways may contribute to the systemic immune dysfunction expressed as cytokines/chemokines dysregulation, a feature clearly emerged from two recent studies on RTT patients. In this light, the purpose of this review is to describe and to stimulate a new discussion on the idea that systemic subclinical inflammation and oxidative stress are crucial players of a detrimental vicious circle, driving the pathogenesis and clinical course of RTT.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cervellati
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. Electronic address: giuseppe.valacchi@unife.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
mesh_terms: D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D015518:Rett Syndrome / Q000503:physiopathology*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Cytokines; Inflammation; MECP2; Oxidative stress; Rett syndrome