DEPDC5, a new key to understand various epilepsies
DEPDC5, a new key to understand various epilepsies
复制标题
DOI：
10.1254/fpj.152.281
复制
发表时间：
2018-12-01
影响因子：
--
通讯作者：
Ishida, Saeko
中科院分区：
文献类型：
--
作者：
Ishida, Saeko
癫痫是最常见的神经系统疾病之一，其特征在于自发性和反复发作。大多数癫痫发作持续一生，患者需要长期治疗。然而，约30%的患者对抗癫痫药物难治。因此，迫切需要更新和更有效的治疗方法。局灶性癫痫，其中异常放电发生在局限于一个半球的神经网络内，占所有成人特发性癫痫病例的约60%。近年来，DEPDC5基因的突变在广泛的局灶性癫痫综合征中有报道。大多数癫痫基因编码离子通道或递质受体，但DEPDC 5与它们没有同源性。DEPDC 5与其他局灶性癫痫相关蛋白NPRL 2和NPRL 3形成一种复合物，称为GATOR 1。GATOR 1抑制mTORC 1通路，调节多种细胞过程，包括细胞生长和增殖。DEPDC 5在神经系统中的作用在最近的动物模型研究中越来越清楚。由于DEPDC5是局灶性癫痫最常见的致病基因，与其他癫痫基因不同，因此DEPDC5将成为了解各种癫痫发病机制的关键，并为开发新的多功能治疗方法提供新的思路。
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.