Structure and Function of Ascaris Neuropeptides

蛔虫神经肽的结构和功能

• 批准号: 7185063
• 负责人: ANTONY O. STRETTON
• 金额: $ 34.71万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7185063
• 关键词: Affect; Affinity; Antibodies; Area; Ascaris; Ascaris suum; Basic Science; Behavior; Biochemical; Caenorhabditis elegans; Cells; Disruption; Dorsal; Drug resistance; Family; Ganglia; Generations; Genetic; Grant; High Pressure Liquid Chromatography; In Situ Hybridization; Indium; Individual; Interneurons; Lasers; Localized; Locomotion; MALDI-TOF Mass Spectrometry; Mass Spectrum Analysis; Mediating; Methods; Molecular; Molecular Biology; Morphology; Motor; Motor Activity; Motor Neurons; Movement; Muscle; Muscle Cells; Muscle Tension; Myxoid cyst; Nematoda; Nerve; Nerve Tissue; Nervous system structure; Neurons; Neuropeptide Gene; Neuropeptides; Paralysed; Parasitic nematode; Peptides; Pharmaceutical Preparations; Physiological; Play; Positioning Attribute; Process; Relaxation; Reporting; Research; Role; Sampling; Signal Transduction; Site; Source; Structure; System; Techniques; Testing; Time; Tissues; Transcript; Work; base; cellular targeting; designer antibody; falls; immunocytochemistry; in vivo; interdisciplinary approach; molecular mass; neuromuscular system; neuronal cell body; novel; protein aminoacid sequence; relating to nervous system; research study

The locomotory system of nematodes is the target of many currently used anthelminthics, since disruption of locomotory behavior interferes with the normal processes by which many nematodes maintain their position within the host. The problem of genetic drug resistance is making many of the available drugs less effective, so it is important to develop new generations of anti-nematdde drugs. The proposed research aims to describe new intercellular signaling systems that are important in the motornervous system that controls locomotion. Our strategy is based on our previous work in which we isolated and sequenced a large family of 29 novel endogenous neuropeptides in the parasitic nematode, Ascaris suum. Preliminary experiments have shown that almost all of the peptides tested have potent activity .on the neuromuscular system of Ascaris. Some cause paralysis, others exaggerate locomotory movements. Neuropeptides, therefore, play an important role in the overall activity of the motornervous system. There is every indication that there are many more peptides than the ones we have isolated so far. There is no indication that the currently available peptides are the most potent, so we propose to isolate new peptides, concentrating on those that are present in the motornervous system, in order to detect new peptides that have potent physiological activity. This is basic research upon which new generations of anthelminthics can ultimately be developed.

线虫的运动系统是许多目前使用的驱虫药的目标，因为 运动行为的破坏会干扰许多线虫在宿主内维持其位置的正常过程。遗传耐药性问题使许多现有药物的疗效降低，因此开发新一代抗线虫药物非常重要。拟议的研究旨在描述新的细胞间信号系统，这些系统在控制运动的运动神经系统中很重要。我们的策略基于我们之前的工作，我们在寄生线虫蛔虫中分离并测序了一个由 29 种新型内源神经肽组成的大家族。初步实验表明，几乎所有测试的肽都对神经肌肉具有有效的活性。 蛔虫系统。有些会导致瘫痪，有些会夸大运动。因此，神经肽在运动神经系统的整体活动中发挥着重要作用。种种迹象表明，肽的数量比我们迄今为止分离出的肽要多得多。没有迹象表明目前可用的肽是最有效的，因此我们建议分离新的肽，重点关注运动神经系统中存在的肽，以检测具有有效生理活性的新肽。这是新一代驱虫药最终能够被开发出来的基础研究。 发达。