Systemic oxidative stress in classic Rett syndrome
Abstract
Rett syndrome (RS), a progressive severe neurodevelopmental disorder mainly caused by de novo mutations in the X-chromosomal MeCP2 gene encoding the transcriptional regulator methyl-CpG-binding protein 2, is a leading cause of mental retardation with autistic features in females. However, its pathogenesis remains incompletely understood, and no effective therapy is available to date. We hypothesized that a systemic oxidative stress may play a key role in the pathogenesis of classic RS. Patients with classic RS (n=59) and control subjects (n=43) were evaluated. Oxidative stress markers included intraerythrocyte non-protein-bound iron (NPBI; i.e., free iron), plasma NPBI, F2-isoprostanes (F2-IsoPs, as free, esterified, and total forms), and protein carbonyls. Lung ventilation/perfusion (V/Q) ratio was assessed using a portable gas analyzer, and RS clinical severity was evaluated using standard scales. Significantly increased intraerythrocyte NPBI (2.73-fold), plasma NPBI (x 6.0), free F(2)-IsoP (x1.85), esterified F2-IsoP (x 1.69), total F2-IsoP (x 1.66), and protein carbonyl (x 4.76) concentrations were evident in RS subjects and associated with reduced (-10.53%) arterial oxygen levels compared to controls. Biochemical evidence of oxidative stress was related to clinical phenotype severity and lower peripheral and arterial oxygen levels. Pulmonary V/Q mismatch was found in the majority of the RS population. These data identify hypoxia-induced oxidative stress as a key factor i…
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Increased oxidative stress has been observed in RTT patients.
“Consistently, altered electron transport chain complex function [27], increased oxidative stress [28–30], and elevated levels of lactate and pyruvate in blood and cerebrospinal fluid [20,27] have been observed in RTT patients (reviewed in [31]).”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [29]
Both RTT patients and Mecp2 mutant mice present with metabolic syndrome, oxidative stress, cardiac defects, decreased bone density and urological dysfunction.
“Additionally, both RTT patients and Mecp2 mutant mice present with metabolic syndrome [15,180], oxidative stress [27,29], cardiac defects [211,212], decreased bone density [174,213] and urological dysfunction [214,215].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [29]
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The isoprostanes—25 years later
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Rett syndrome: a neurological disorder with metabolic components
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“…(Ruch et al., 1989; Wakai et al., 1990; Dotti et al., 1993; Cornford et al., 1994), enzymatic defects of the mitochondrial respiratory chain (Eeg-Olofsson et al., 1989; Coker and Melnyk, 1991; Heilstedt et al., 2002), and increased oxidative stress (Sierra et al., 2001; De Felice et al., 2009).”
BackgroundScavenger receptor B1 post-translational modifications in Rett syndrome
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Self-citationRedox imbalance and morphological changes in skin fibroblasts in typical Rett syndrome
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Self-citationOxidative stress in developmental brain disorders
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Modulation of Brain Cholesterol Metabolism through CYP46A1 Overexpression for Rett Syndrome
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- Authors
- De Felice, C., Ciccoli, L., Leoncini, S., Signorini, C., Rossi, M., Vannuccini, L., Guazzi, G., Latini, G., Comporti, M., Valacchi, G., & Hayek, J.
- Affiliations
- University of Siena (IT)
- Azienda Ospedaliera Universitaria Senese (IT)
- Istituto di Fisiologia Clinica (IT)
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 47
- Issue
- 4
- Pages
- 440-448
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2051460287
- Cited by
- 148
- References
- 3
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 10 · 2022: 5 · 2021: 11 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 12 · 2016: 8 · 2015: 13 · 2014: 15 · 2013: 12 · 2012: 11
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Rett syndrome, oxidative stress, MeCP2, non-protein-bound iron, F2-isoprostanes, protein carbonyls, hypoxia, clinical severity
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Erythrocytes, Female, Humans, Iron, Intellectual Disability, Mutation, Oxygen, Ventilation-Perfusion Ratio, Rett Syndrome, Oxidative Stress, Disease Progression, Genetic Predisposition to Disease, F2-Isoprostanes, Protein Carbonylation, Methyl-CpG-Binding Protein 2
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