NOVEL NEURONAL NACHR-TARGETED PEPTIDES

描述(摘自申请者的摘要)：烟碱型乙酰胆碱 受体(NAChRs)是一类配体门控离子通道，发现于 神经肌肉连接和整个中枢神经系统。中枢刺激 尼古丁受体似乎能提高正常人的注意力和注意力 个人和nAChRs与几种神经精神疾病有牵连 疾病包括抽动症、阿尔茨海默病、精神分裂症、 迟发性运动障碍和帕金森氏症。分子生物学已经表明 神经元nAChRs有许多亚型。不幸的是， 不同的中枢神经系统受体亚型的功能作用尚未得到 勾勒出来的。 被称为圆锥的大量肉食性海洋蜗牛的毒液含有 数以千计的神经活性多肽，其中许多似乎针对nAChRs。 这项资助的主要目的是应用强大的神经生物学 向着亚型特异性nAChR靶向库的方向发展 多肽。在初步研究中，一种这样的多肽，α-芋螺毒素IMI具有 已被分离、合成，并被证明是含有7-的特异性的 神经元nAChRs。更多的研究表明，圆锥体毒液含有其他 针对其他神经元亚型的nAChRs的多肽。《少年派》 将使用在卵母细胞中表达的克隆nAChRs和其他方法来检测 并分离新的nAChR靶向多肽。纯化的多肽将是 生物化学表征和合成。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 确定新配体的亚型特异性。这样的配体将会 极大地帮助研究人员确定其功能作用和意义 神经精神健康和疾病中的神经元nAChRs。

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.