NOVEL PROTECTIVE NEUROPHILINS IN IDIOPATHIC PARKINSON'S DISEASE

特发性帕金森病中的新型保护性嗜神经蛋白

• 批准号: 6478907
• 负责人: OLE ISACSON
• 金额: $ 5.36万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6478907
• 关键词: Macaca fascicularis; Parkinson's disease; behavior test; brain imaging /visualization /scanning; brain metabolism; chemoprevention; chordate locomotion; disease /disorder model; dopamine; dopamine transporter; glucose metabolism; magnetic resonance imaging; methylphenyltetrahydropyridine; nervous system regeneration; neural degeneration; neuropharmacology; neuroprotectants; neurotoxicology; neurotoxins; neurotrophic factors; nonhuman therapy evaluation; peptidylprolyl isomerase; positron emission tomography; postmortem

As humans age, a recent large PD twin study indicates that physiological and toxic factors play major roles in causing typical PD, This progressive decline of dopamine (DA) terminals seen in idiopathic PD can be closely modeled in Macaca fascicularis by a low-dose exposure to the mitochondrial toxin, MPTP, over nine to fourteen months. The PET imaging of DA terminal and MRS data from such animals provide a physiological chart of degeneration and appearance of PD signs. This data profile enables the design of an experimental paradigm for realistically determining neuroprotection and regeneration in idiopathic PD. Based on our novel findings of neurophilin (V-10, 367) prevention of MPTP-induced toxicity in mice and DA degeneration in rat, we propose to examine 2 hypotheses. First, by delivering the neurophilin in parallel with MPTP, we can substantially delay the onset of PD signs. Second, by starting neurophilin treatment after PD signs (post-MPTP paradigm) we can prevent the continued DA and physiological decline and possibly reverse the parkinsonism. This project will generate unique data about the physiology of parkinsonism. This project will generate unique data about the physiology of parkinsonism and novel neurophilin prevention and reversal of DA degeneration seen in PD.

随着人类年龄的增长，最近的一项大型 PD 双胞胎研究表明，生理和毒性因素在引起典型 PD 中发挥着重要作用。特发性 PD 中观察到的多巴胺 (DA) 末端的逐渐下降可以通过低剂量暴露在食蟹猴中密切模拟。线粒体毒素 MPTP，需要九到十四个月的时间。 DA 终端的 PET 成像和来自此类动物的 MRS 数据提供了退化和 PD 体征出现的生理图表。该数据概况可以设计一个实验范例，以实际确定特发性帕金森病的神经保护和再生。基于我们对亲神经素 (V-10, 367) 预防 MPTP 诱导的小鼠毒性和大鼠 DA 变性的新发现，我们建议检验 2 个假设。首先，通过与 MPTP 并行输送亲神经素，我们可以大大延迟 PD 症状的出现。其次，通过在 PD 症状后开始亲神经素治疗（MPTP 后范例），我们可以防止持续的 DA 和生理下降，并可能逆转帕金森病。该项目将生成有关帕金森病生理学的独特数据。该项目将生成有关帕金森病生理学的独特数据，以及新型亲神经素预防和逆转帕金森病中所见的 DA 变性。