Quantitative proteomic alterations of human iPSC-based neuronal development indicate early onset of Rett syndrome.
Rett syndrome (RTT) is a progressive neurodevelopmental disease often caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). The mechanisms by which impaired MeCP2 induces the pathological abnormalities in the brain is not understood. To understand the molecular mechanisms involved in disease onset, we used an RTT patient induced pluripotent stem cell (iPSC)-based model and applied an in-depth high-resolution quantitative mass spectrometry-based analysis during early stages of neuronal development. Our data provided evidence of proteomic alteration at developmental stages long before the phase that symptoms of RTT syndrome become apparent. Differential expression increased from early to late neural stem cell phases, although proteins involved in immunity, metabolic processes and calcium signaling were already affected at initial stages. This data can help development of new biomarkers and therapeutic approaches in RTT syndrome.
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