[DEPDC5, a new key to understand various epilepsies]

Epilepsy is one of the most frequent neurological disorders characterized by spontaneous and recurrent seizures. Most seizures last for the lifetime and the patients require long term therapies. However, about 30% of the patients are refractory to antiepileptic drugs. Therefore, the need for newer and more effective therapies is urgent. Focal epilepsies, in which the abnormal electrical discharges occur within neuronal networks limited to one hemisphere, accounts for about 60% of all adult idiopathic epilepsy cases. Recently, mutations of DEPDC5 gene has been reported in wide spectrum of focal epilepsy syndromes. Most epilepsy genes encode ion channel or transmitter receptor, but DEPDC5 has no homology with them. DEPDC5 forms a complex, named GATOR1, together with other focal epilepsy related proteins NPRL2 and NPRL3. GATOR1 inhibits the mTORC1 pathway, regulating multiple cellular processes including cell growth and proliferation. The role of DEPDC5 in neuronal system is becoming clear from recent studies using the animal models. Because DEPDC5 is the most common causative gene in focal epilepsies and different from other epilepsy genes, DEPDC5 will be a key to understand epileptogenesis of various epilepsies, and provide new insight to develop new versatile therapies.