Scheme 1.

Schematic summary related to the altered gene expression observed in RTT PBMC. MeCP2 in a normal situation binds to several cofactors (Sin3A, CREB1, etc.) to regulate gene transcription. Mutation of MeCP2 (crossed boxes) will affect gene expression leading to a gene profile deregulation. There are mainly 4 gene clusters significantly affected in RTT PBMC, that is, those related to chromatin folding (1), mitochondrial functions (2), ubiquitin-proteasome (3), and antioxidant defence (4) (green boxes). The overexpression of the genes involved in ATP synthesis processes (2) can be interpreted as a possible energy requirement for an increment of cellular protein degradation (3), consequent to increased mitochondrial ROS production and protein oxidation. The increased expression of the “antioxidant cellular defence” genes (4) is the possible compensatory mechanism activated by the cells to quench ROS production and protein oxidation (red arrows).