日本自然科学研究机构生理学研究所26日发布公报说，该机构研究人员与美国同行发现，正常实验鼠体内的3种蛋白质能组成“抗癫痫蛋白质复合体”，精密调节脑内的突触传递，从而防止癫痫的发病。
公报说，生理学研究所深田优子副教授的研究小组和美国加利福尼亚大学旧金山分校的同行发现，神经细胞之间相互接触的部位——神经突触存在一种特殊的分泌蛋白质“LGI1”，这种蛋白质能与另外两种与癫痫相关的蛋白质“ADAM22”、“ADAM23”相结合，形成“抗癫痫蛋白质复合体”，使神经突触保持正常功能，避免发生癫痫。
在实验中，研究人员通过基因技术使实验鼠不能合成“LGI1”蛋白质，结果在“抗癫痫蛋白质复合体”也无法形成的情况下，实验鼠的神经突触出现功能异常，引发了癫痫病。特别是在掌管记忆的大脑海马部位，由于“LGI1”蛋白质的消失，神经突触的信号传递方式也出现异常。
公报说，癫痫是一种较常见的神经疾病，发病者数量占世界人口的1％。通常认为癫痫由神经细胞的异常兴奋引起，但其病因尚未被完全破解，也没有根本的治疗方法。本项研究表明，有可能通过补充“LGI1”蛋白质或者负责编码这种蛋白质合成的基因来治疗部分癫痫患者。（生物谷Bioon.com）
生物谷推荐原文出处：
PNAS Published online before print February 2, 2010, doi: 10.1073/pnas.0914537107
Disruption of LGI1–linked synaptic complex causes abnormal synaptic transmission and epilepsy
Yuko Fukataa,b, Kathryn L. Loveroc, Tsuyoshi Iwanagaa, Atsushi Watanabed, Norihiko Yokoia, Katsuhiko Tabuchie, Ryuichi Shigemotoe,f, Roger A. Nicollc, and Masaki Fukataa,1
Epilepsy is a devastating and poorly understood disease. Mutations in a secreted neuronal protein, leucine-rich glioma inactivated 1 (LGI1), were reported in patients with an inherited form of human epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF). Here, we report an essential role of LGI1 as an antiepileptogenic ligand. We find that loss of LGI1 in mice (LGI1?/?) causes lethal epilepsy, which is specifically rescued by the neuronal expression of LGI1 transgene, but not LGI3. Moreover, heterozygous mice for the LGI1 mutation (LGI1+/?) show lowered seizure thresholds. Extracellularly secreted LGI1 links two epilepsy-related receptors, ADAM22 and ADAM23, in the brain and organizes a transsynaptic protein complex that includes presynaptic potassium channels and postsynaptic AMPA receptor scaffolds. A lack of LGI1 disrupts this synaptic protein connection and selectively reduces AMPA receptor–mediated synaptic transmission in the hippocampus. Thus, LGI1 may serve as a major determinant of brain excitation, and the LGI1 gene-targeted mouse provides a good model for human epilepsy.
