Identification of differentially phosphorylated proteins in the brain tissue resected from patients with mesial temporal lobe epilepsy with hippocampal sclerosis

Abstract

Epilepsy is a chronic neurological disorder affecting around 2% of the world population. It presents with a wide variety of clinic manifestation, etiologies, severity, and prognosis. However, the occurrence of an epileptic seizure, caused by abnormal neuronal discharges, is the characteristic feature of all types of epilepsy. Mesial temporal lobe epilepsy (MTLE) is the most frequent form in adults, and it is present in about 40% of the patients with epilepsy, many of whom do not respond well to clinical treatment. Epilepsy surgery is a well-recognized treatment option for many patients with MTLE and refractory seizures, and the tissue resected during surgery can be subsequently studied. In 2013 we established an epilepsy brain bank containing tissue samples of all patients undergoing epilepsy surgery at the University of Campinas (UNICAMP) hospital. This was established within the scope of the Brazilian Institute of Neuroscience and Neurotechnology (www.brainn.org.br). To date, we have hundreds of tissue samples obtained from very well characterized patients with different types of epilepsy. In this project, we aim to perform large-scale phosphoproteomics in tissue from patients with MTLE. The proteome refers to all proteins that are expressed by a cell, tissue or organism under defined conditions, at a certain time. It is well known that protein phosphorylation regulates several important functions, including brain development and normal neuronal activity. With large-scale phosphoproteomics, it is now possible to identify phosphorylation sites from tissues at distinct stages, leading to new insights into the mechanisms of many human disorders. With the successful completion of this project, we expect to identify key proteins which are differentially expressed in tissue from patients, indicating neurobiological pathways that may be relevant for the etiology of MTLE.