Abstract
Rett syndrome (RTT) is a rare and severe neurodevelopmental disorder, mainly caused (~90-95% of cases) by loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 gene. Recent studies indicate an important role of oxidative stress in damaging the RTT erythrocytes. The present study aims at demonstrating that the abnormal erythrocyte morphology observed in RTT (i.e., leptocytosis) is related to protein expression changes and oxidative posttranslational modifications (PTMs). Furthermore, we evaluated whether protein changes could be rescued following ω-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation. Erythrocytes from RTT patients, either on or off ω-3 PUFAs, were examined for oxidative PTMs, protein expression, protein-protein interaction and biophysical parameters. Significant (P < 0.05) expression changes and oxidative PTMs for 12 proteins were evidenced in RTT, and related to increased susceptibility of erythrocytes to mechanical stress (i.e., spectrin alpha and beta chains, ankyrin, band 3, protein 4.1, adducin, protein 4.2, 55 kDa protein, beta-actin, tropomodulin, aldolase and glyceraldehyde-3-phosphate dehydrogenase). Half of these proteins were rescued after ω-3 PUFAs supplementation. Our findings indicate the occurrence of a significant disruption in the RTT erythrocyte cytoskeletal-membrane protein network as the result of redox imbalance and protein expression changes, which appear to be partially rescued by ω-3 PUFAs.