The MECP2 protein controls the activity of hundreds of genes in neurons. When mutations cause loss of its activity appears Rett syndrome, a disease of neurodevelopment which is the second most common cause of mental retardation in females after Down syndrome.

An increased activity of MECP2 could also alter neurons as men with extra copies of this gene also exhibit mental retardation. Which mechanisms are acting in this case? The laboratory of Manel Esteller, Director of Epigenetics and Cancer Biology, Bellvitge Biomedical Research Institute (IDIBELL) , ICREA researcher and Professor of Genetics at the University of Barcelona, ​​has overexpressed the MECP2 protein in neurons and has been shown to cause significant neuronal damage. The findings are published in the online edition of the journal Neurobiology of Disease.

“MECP2 acts as a great light switch to turn on or off genes in neurons. Girls with Rett syndrome have a defect in the gene off, while men with mental retardation have the lights open all day” says Manel Esteller.

” What we have seen in relation to this condition, is that to have an excess of MECP2 causes the cells from which neurons grow, called neuroblasts, stop dividing and die more besides, so their total number reduced. Also, some neurones are placed in sites of the nervous system where they should not. The sum of these changes explains neurological alterations when an individual experiences an overdose of MECP2.”

“Although the results provide significant insight into the mechanisms involved in Rett Syndrome and Mental Retardation Associated with Extra Copies of MECP2, we are still far from finding an effective therapy for these diseases, but every great journey begins with first step, ” concludes the researcher.

Article reference

Petazzi P, Akizu N, Garcia A, Estarás C, Martinez de Paz A, Rodríguez-Paredes M, Martínez-Balbás M, Huertas D, Esteller M. An Increase in MeCP2 Dosage Impairs Neural Tube Formation. Neurobiology of Disease, DOI: 10.1016/j.nbd.2014.03.009, 2014.