日本自然科學研究機構(gòu)生理學研究所26日發(fā)布公報說,，該機構(gòu)研究人員與美國同行發(fā)現(xiàn)，正常實驗鼠體內(nèi)的3種蛋白質(zhì)能組成“抗癲癇蛋白質(zhì)復合體”,，精密調(diào)節(jié)腦內(nèi)的突觸傳遞,，從而防止癲癇的發(fā)病。
公報說,，生理學研究所深田優(yōu)子副教授的研究小組和美國加利福尼亞大學舊金山分校的同行發(fā)現(xiàn),，神經(jīng)細胞之間相互接觸的部位——神經(jīng)突觸存在一種特殊的分泌蛋白質(zhì)“LGI1”，這種蛋白質(zhì)能與另外兩種與癲癇相關(guān)的蛋白質(zhì)“ADAM22”,、“ADAM23”相結(jié)合,，形成“抗癲癇蛋白質(zhì)復合體”，使神經(jīng)突觸保持正常功能,，避免發(fā)生癲癇。
在實驗中,，研究人員通過基因技術(shù)使實驗鼠不能合成“LGI1”蛋白質(zhì),，結(jié)果在“抗癲癇蛋白質(zhì)復合體”也無法形成的情況下，實驗鼠的神經(jīng)突觸出現(xiàn)功能異常,，引發(fā)了癲癇病,。特別是在掌管記憶的大腦海馬部位，由于“LGI1”蛋白質(zhì)的消失,，神經(jīng)突觸的信號傳遞方式也出現(xiàn)異常,。
公報說，癲癇是一種較常見的神經(jīng)疾病,，發(fā)病者數(shù)量占世界人口的1％,。通常認為癲癇由神經(jīng)細胞的異常興奮引起，但其病因尚未被完全破解,，也沒有根本的治療方法,。本項研究表明，有可能通過補充“LGI1”蛋白質(zhì)或者負責編碼這種蛋白質(zhì)合成的基因來治療部分癲癇患者,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
