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.