Molecular Mechanisms behind Initiation of Focal Seizure in Temporal Lobe Epilepsy: Computational Study

Abstract

Epilepsy is a noncommunicable disease of the brain that affects people of all ages. The chapter aims to identify protein targets and their mechanism of action behind temporal lobe epilepsy. Differentially expressed proteins in temporal lobe epilepsy (TLE) were used to derive a hypothesis demonstrating routes of protein interactions causing focal seizure and identification of putative target receptor for its treatment. Text mining was done by constructing a Boolean query with keywords such as temporal lobe epilepsy, focal seizures, proteomics, etc., in different scientific search engines. The proteins were further used for creating protein interaction network and analysed for their role in focal epileptic seizure pathway. The most appropriate route for initiation of seizure was observed to be route 3. It describes the dysregulated signal transduction from adenosine A1 receptor (ADORA1) to gamma-aminobutyric acid (GABA) B receptor 1 (GABBR1). This causes electrical imbalance and hyper-excitation of neurons that lead to focal seizure. The study also predicts that YWHAZ (3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) could be the potential target for preventing focal seizures. The network framed in this study is ideal for studying the cascades of events that may occur during focal seizures in TLE and is useful in drug discovery.