SIGNAL TRANSDUCTION MECHANISMS IN GLUTAMATE TOXICITY

某些急性侮辱和慢性神经退行性变的病因 由于发现这些疾病可能是 全部或部分通过谷氨酸受体激活表现出来的。这些 疾病包括中风、阿尔茨海默氏症和亨廷顿氏症。 不幸的是，人们对细胞内机制知之甚少。 负责谷氨酸诱导的细胞死亡。分子的力量 遗传学将被用于探索信号转导机制。这个 蛋白激酶C的催化或调节(抑制)结构域， 钙/钙调素依赖的蛋白激酶II和钙激活 利用HSV-1在培养神经元中表达中性蛋白水解酶 向量系统。然后，被感染的细胞将受到有毒剂量的 不同的谷氨酸激动剂来确定这些酶在 调节神经细胞的死亡。单纯疱疹病毒1型载体系统的研制 研究谷氨酸的神经毒性可能具有广泛的影响：1)和 对这些细胞内过程的理解可能提示临床 中风的治疗策略。2)HSV-1载体可能提供一种新的 康复治疗慢性神经系统疾病的方法探讨 通过基因疗法发挥作用。

The etiology of certain acute insults and chronic neuro-degenerative disorders has been advanced by the finding that these diseases are possibly manifested fully or in part through glutamate receptor activation. These diseases include stroke, Alzheimer's and Huntington's disease. Unfortunately, very little is known about the intracellular mechanisms responsible for glutamate-induced cell death. The power of molecular genetics will be used to probe signal transduction mechanisms. The catalytic or regulatory (inhibitory) domain of protein kinase C, calcium/calmodulin-dependent protein kinase II, and calcium activated neutral proteinase will be expressed in cultured neurons using a HSV-1 vector system. Infected cells will then be challenged with toxic doses of various glutamate agonists to determine the role of these enzymes in mediating neuronal death. The development of the HSV-1 vector system to study glutamate neurotoxicity could have broad implications: 1) An understanding of these intracellular processes may suggest clinical therapeutic strategies for stroke. 2) The HSV-1 vector may provide a novel therapeutic approach in treating chronic neurologic disorders by restoring function through gene therapy.