NOVEL NEURONAL NACHR-TARGETED PEPTIDES

新型神经元 NACHR 靶向肽

• 批准号: 2416091
• 负责人: J MICHAEL MCINTOSH
• 金额: $ 9.97万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2416091
• 关键词: Hermissenda; Xenopus oocyte; neurotoxins; nicotinic receptors; peptide chemical synthesis; receptor binding; toxicant screening

DESCRIPTION (Adapted from applicant's abstract): Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels found at the neuromuscular junction and throughout the CNS. Stimulation of central nicotinic receptors appears to enhance concentration and attention in normal individuals and nAChRs have been implicated in several neuropsychiatric disorders including Tourette's syndrome, Alzheimer's disease, schizophrenia, tardive dyskinesia, and Parkinson's disease. Molecular biology has shown that there are numerous subtypes of neuronal nAChRs. Unfortunately, the functional role of each of the diverse CNS receptor subtypes has not been delineated. Venom from the numerous carnivorous marine snail known as Conus contain thousands of neuroactive peptides, many of which appear to target to nAChRs. The major goal of this grant is the application of the powerful neurobiology of Conus toward the development of a bank of subtype-specific nAChR-targeted peptides. In preliminary studies, one such peptide, alpha-conotoxin ImI has been isolated, synthesized, and shown to be specific for a 7-containing neuronal nAChRs. Additional studies show that cone venoms contain other peptides which target to additional neuronal subtypes of nAChRs. The PI will use cloned nAChRs expressed in oocytes and additional methods to detect and isolate novel nAChR-targeted peptides. Purified peptides will be biochemically characterized and synthesized. The oocyte expression system as well as radiolabeling and receptor binding techniques will be used to determine the subtype specificity of the novel ligands. Such ligands would greatly help researchers determine the functional role and significance of neuronal nAChRs in neuropsychiatric health and disease.

描述（改编自申请人的摘要）：烟碱乙酰胆碱 受体 (nAChR) 是一个配体门控离子通道家族，存在于 神经肌肉接头和整个中枢神经系统。 Stimulation of central 烟碱受体似乎可以增强正常人的注意力和注意力 个体和 nAChR 与多种神经精神疾病有关 疾病包括图雷特氏综合症、阿尔茨海默病、精神分裂症、 迟发性运动障碍和帕金森病。 分子生物学表明 神经元 nAChR 有多种亚型。 不幸的是， 每种不同 CNS 受体亚型的功能作用尚未明确 delineated. 来自众多肉食性海洋蜗牛（称为 Conus）的毒液含有 数千种神经活性肽，其中许多似乎以 nAChR 为目标。 这笔赠款的主要目标是强大的神经生物学的应用 Conus 致力于开发亚型特异性 nAChR 靶向库 肽。 在初步研究中，一种这样的肽，α-芋螺毒素 ImI 已被分离、合成并显示对含 7 的 neuronal nAChRs. 其他研究表明，锥体毒液还含有其他成分 靶向 nAChR 的其他神经元亚型的肽。 PI 将使用卵母细胞中表达的克隆 nAChR 和其他方法来检测 并分离新型 nAChR 靶向肽。 纯化的肽将是 生化表征和合成。 卵母细胞表达系统 以及放射性标记和受体结合技术将用于 确定新型配体的亚型特异性。 Such ligands would 极大地帮助研究人员确定其功能作用和意义 神经元 nAChR 在神经精神健康和疾病中的作用。