EXCITATORY AA RECEPTORS' IN ALZHEIMER'S AND OTHER NEURODEGENERATIVE DISORDERS

阿尔茨海默病和其他神经退行性疾病中的兴奋性 AA 受体

• 批准号: 2565705
• 负责人: J W KUSIAK
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2565705
• 关键词: Alzheimer's disease; NMDA receptors; aging; biological signal transduction; excitatory aminoacid; fibroblast growth factor; genetic promoter element; glutamate receptor; glutamates; laboratory mouse; molecular cloning; neural degeneration; neurotrophic factors; receptor expression; tissue /cell culture

Excitatory amino acids and their receptors play many important physiological roles in the central nervous system. They are involved in brain development, neural plasticity, memory acquisition, and excitotoxicity. The goal of this project is to determine the mechanisms responsible for transcriptional control of the NMDA subtype of glutamate receptor genes. Promoter regions of the genes from several family members were cloned. Similarities were found in gene structure and transcriptional control elements. NGF activates expression of the NMDAR1 gene via its high affinity Trk A receptor and this activation requires the presence of both Sp1 and GSG transcriptional elements in the proximal promoter region. Over-expression of NGFI-A, also induced by NGF, activates NMDAR1 gene expression suggesting a signal transduction pathway for gene activation involving immediatae early genes.

兴奋性氨基酸及其受体发挥许多重要的作用 中枢神经系统的生理作用。他们参与了 大脑发育，神经可塑性，记忆的获取和 兴奋性毒性。该项目的目的是确定机制 负责谷氨酸NMDA亚型的转录控制 受体基因。来自几个家庭成员的基因的发起人区域 被克隆。在基因结构中发现了相似之处， 转录控制元素。 NGF激活NMDAR1的表达 基因通过其高亲和力TRK A受体，并且这种激活需要 近端中SP1和GSG转录元件的存在 启动子区域。 NGF的过表达，也是由NGF诱导的 激活NMDAR1基因表达，提示信号转导途径 用于涉及直接基因的基因激活。