Neurotrophins and Epileptogenesis

项目摘要 缺乏对人类常见疾病的预防和疾病改善治疗 神经系统是一个明显的未满足的医疗需求，对NINDS的使命至关重要。工作 提出了一种新的方法来揭示分子信号机制 潜在的颞叶癫痫（TLE）。本供资期间完成的工作 揭示了脑源性神经营养因子（BDNF）受体酪氨酸的关键作用， TrkB在癫痫持续状态诱发的TLE发展中的作用TrkB介导的激活 磷脂酶C β 1是TrkB促进细胞凋亡的主要途径。 TLE的发展。本申请的目的是探索TrkB在细胞内的作用。 信号在TLE的持续性中。为了达到这个目标，我们将研究 TrkB信号转导对不同癫痫患者诱导的癫痫的药理学和遗传学干扰 TLE模型成功完成拟议的工作可能会为预防性 和/或改善TLE（一种常见的人类中枢神经系统疾病）的疾病治疗 系统

Project Summary Lack of preventive and disease modifying treatments for common disorders of the human nervous system is a glaring unmet medical need critical to the mission of NINDS. The work proposed here represents a novel approach to uncover molecular signaling mechanisms underlying temporal lobe epilepsy (TLE). Work accomplished during the current funding period reveals a pivotal role for the brain-derived neurotrophic factor (BDNF) receptor tyrosine kinase,TrkB, in the development of TLE induced by status epilepticus. TrkB-mediated activation of the effector, phospholipase C1, is the dominant pathway by which TrkB promotes development of TLE. The objective of the current application is to explore the role of TrkB signaling in the persistence of TLE. To accomplish this objective, we will examine the effect of pharmacological and genetic perturbations of TrkB signaling on epilepsy induced in diverse models of TLE. Successful completion of the work proposed may pave the way to preventive and/or disease modifying therapy of TLE, a common disorder of the human central nervous system.