Potassium Channel Gene Therapy to Prevent Neuron Death

钾通道基因疗法预防神经元死亡

• 批准号: 6445444
• 负责人: ANGELA L LEE
• 金额: $ 4.62万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6445444
• 关键词: apoptosis; behavior test; biotechnology; calcium flux; cell death; disease /disorder model; electrophysiology; epilepsy; gene expression; gene therapy; hippocampus; ischemia; laboratory rat; learning; memory; necrosis; neurons; neuroprotectants; neurotoxicology; postdoctoral investigator; potassium channel; stereotaxic techniques; technology /technique development; tissue /cell culture; transfection /expression vector; voltage gated channel

DESCRIPTION (Verbatim from applicant?s abstract): Although gene therapy been shown to be a promising strategy for excitotoxic insults in the brain, currently used vectors do not express functional protein soon enough after insult to target the earliest events reading to necrotic neuronal injury. This proposal tests a novel strategy: constitutive expression of a potentially protective protein whose activity would be activated by insult. Seizures are, by definition, excitotoxic, and decreasing such excitation might be neuroprotective. This might be accomplished by hyperpolarizing excited neurons via outwardly rectifying potassium (K+) channels, thus prolonging the recovery phase of the action potential and/or shortening spike duration. The protective effects of a Ca2+-regulated or a voltage-gated K+ channel will be explored. In pilot data we have shown that both protect in primary hippocampal cultures against glutamate, staurosporine, and sodium cyanide. We will extend these findings by testing more insults as well as exploring the extent to which protection targets necrosis vs. apoptosis. In vivo studies will not only examine whether there is sparing of neuron number, but of function as well (using electrophysiological and behavioral endpoints). Finally, we will examine the activity of these channels in healthy neurons and, if they are active, test their effects on normal learning and memory.

描述（来自申请人？）尽管基因疗法一直被人们所关注