Neurological diseases: molecular defects in lissencephaly and epileptic encephalopathy identified at the CNR
A study directed by Maria Giuseppina Miano dell‘”Adriano Buzzati-Traverso” Institute of Genetics and Biophysics the National Research Council (Cnr-Igb), identifies the damaged functions in two serious neurological diseases such as lissencefalia and theepileptic encephalopathy development, caused by different mutations of the gene ARX whose role is fundamental for correct brain development. The study was published in the journal Human Molecular Genetics and performed in collaboration with the Department of Molecular Medicine and Medical Biotechnology dell’University of Naples “Federico II (Unina), the research and molecular diagnostics center Advanced Ceinge-Biotechnology of Naples and theInstitute of Biosciences and Bioresources the National Research Council (Cnr-Ibbr)and with the support of Telethon Foundation.
Neurological diseases: the basis for new therapeutic approaches in children discovered
Thanks to an integrated approach that combines proteomics studies with in vivo analyzes, the research team established what happens in the presence of a mutation that abolishes or modifies the functions of the ARX protein. The research, conducted in mutant animal models, reveals what happens in the cells of the diseased brain as a consequence of one or the other mutation, highlighting at the same time the alteration of numerous functional processes, some of which shared, others strictly dependent on the type of mutation.
“The large amount of data obtained from the proteomics investigation has made it possible to shed light on the functions damaged in case of lissencefalia o di epileptic encephalopathy“, explains Denise Drongitis the Cnr-Igb and first author of the study. “Starting from the anomalous amount of thousands of proteins, we defined the altered processes in each genetic condition analyzed”, he adds. Marianna Caterino Of Unina/Ceinge and another first author of the study. “Thanks to proteomics studies and in vivo analyzes, we found that mutations in the ARX gene alter unexpected molecular and cellular functions – such as the organization of the microtubule cytoskeleton, the alternative splicing of the Neurexin 1 and 2 genes and the control of protein synthesis. “, he concludes Maria Giuseppina Miano the Cnr-Igb. “We have also shown how these functions are particularly damaged in neurons of the cortex, establishing completely new aspects of lissencephaly and epileptic encephalopathy”.
These findings further help understand the pathogenesis of these diseases and open up new studies to identify therapeutic targets and improve the condition of children with ARX mutations.