Opioid Receptor Polymorphism & PD Drug Response

阿片受体多态性

• 批准号: 7223339
• 负责人: LEI YU
• 金额: $ 14.04万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2008-02-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7223339
• 关键词: Parkinson' s disease; Xenopus; brain disorder chemotherapy; genetic polymorphism; genetic promoter element; human subject; human therapy evaluation; levodopa; molecular cloning; opioid receptor; patient oriented research; pharmacogenetics; receptor binding; receptor expression

DESCRIPTION: (Verbatim from the Applicant's Abstract) Parkinson's disease (PD) is a common movement disorder with tremor, rigidity, and bradykinesia. The central event in PD is the loss of the dopaminergic inputs to the basal ganglia. The disease is characterized by great variability from patient to patient in the course of the disease, the relative predominance of various symptoms, the response to L-DOPA therapy, and the development of dyskinesias during L-DOPA therapy. Studies exploring the ramifications of the dopamine deficiency in PD have provided increasing evidence that changes in the other basal ganglia neurotransmitter systems, in particular the opioid system, may also play a role in the disease process. This evidence includes PET scan studies in PD patients that showed correlations between dyskinesias and altered opioid binding levels, as well as work in animal models sugggesting the involvement of opioid system in the development of dyskinesias during L-DOPA therapy. In this revised application, the basic hypothesis we propose to test is that some of the observed variability in PD patient's symptoms and response to L-DOPA may be related to an underlying genetic variation in opioid receptors. We propose to study genetic polymorphism of the mu opioid receptor in PD patients, and to characterize at a cellular level the consequences of these polymorphisms on receptor expression level and receptor function. The specific aims of the proposal are: 1. To identify genetic polymorphisms in both the promoter and the coding region of the mu opioid receptor in PD patients and to determine whether any of the polymorphisms are associated with variations in clinical symptoms and outcomes: 2.) To determine the effect of the coding region polymorphisms on both ligand binding properties of the receptor and receptor-mediated cellular functions; and 3.) To determine the effect of promoter sequence polymorphisms on the expression levels of the receptor. Such functional studies are essential in moving from association to causality. Our preliminary studies of 26 PD patients have identified a mu opioid receptor polymorphism in the PD population. This polymorphism was significantly associated with the clinical outcome of L-DOPA therapy-induced dyskinesia. Further studies in a larger PD patient cohort may identify additional polymorphisms of interest, and may provide predictor for clinical management of PD.

描述：(逐字摘自申请者摘要)帕金森氏症(PD) 是一种常见的运动障碍，伴有震颤、僵硬和运动迟缓。这个 帕金森病的中心事件是基础多巴胺能输入的丢失 神经节。这种疾病的特点是患者之间的差异很大。 患者在病程中，相对优势的各种 症状、对L多巴治疗的反应和运动障碍的发展 在L-多巴治疗期间。探索多巴胺的分支的研究 帕金森病的缺乏提供了越来越多的证据表明 基底节神经递质系统，特别是阿片系统，可以 也在疾病过程中发挥作用。这一证据包括PET扫描 对帕金森病患者的研究表明运动障碍和改变之间存在相关性 阿片结合水平，以及在动物模型中的工作表明 阿片系统参与L多巴训练中运动障碍的发生 心理治疗。 在这个修订后的应用程序中，我们建议测试的基本假设是 帕金森病患者症状和反应中的一些观察到的变异性 L多巴可能与阿片受体的潜在遗传变异有关。 我们建议在帕金森病患者中研究u阿片受体的遗传多态性。 并在细胞水平上表征这些疾病的后果 受体表达水平和受体功能的多态。具体的 这项建议的目的是：1.确定两个群体的遗传多态 帕金森病患者mU阿片受体启动子和编码区的研究 确定是否有任何多态与 临床症状和转归：1)确定编码的效果 受体和受体配体结合特性的区域多态性 受体介导的细胞功能；确定……的效果 启动子序列多态性对受体表达水平的影响。是这样的 从关联到因果关系，功能研究是必不可少的。 我们对26例帕金森病患者的初步研究已经确定了一种u阿片受体。 帕金森病患者的基因多态性。这种多态现象显著地 与L多巴治疗所致运动障碍的临床转归有关。 在更大规模的PD患者队列中进行的进一步研究可能会发现 感兴趣的基因多态性，并可能为临床治疗提供预测因子 警察。

项目成果

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.

SIP30 在周围神经损伤引起的神经性疼痛的发生和维持中的作用

• DOI: 10.1016/j.pain.2009.07.011
• 发表时间: 2009-11
• 期刊: Pain
• 影响因子: 7.4
• 作者: Zhang YQ;Guo N;Peng G;Wang X;Han M;Raincrow J;Chiu CH;Coolen LM;Wenthold RJ;Zhao ZQ;Jing N;Yu L
• 通讯作者: Yu L

Effects of naltrexone on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J mice.

• DOI: 10.1016/j.pnpbp.2013.03.002
• 发表时间: 2013-07-01
• 期刊: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
• 影响因子: 5.6
• 作者: Tomie, Arthur;Azogu, Idu;Yu, Lei
• 通讯作者: Yu, Lei

rSac3, a novel Sac domain phosphoinositide phosphatase, promotes neurite outgrowth in PC12 cells.

rSac3 是一种新型 Sac 结构域磷酸肌醇磷酸酶，可促进 PC12 细胞中的神经突生长。

• DOI: 10.1038/cr.2007.82
• 发表时间: 2007
• 期刊: Cell research
• 影响因子: 44.1
• 作者: Yuan,Yiyuan;Gao,Xiang;Guo,Ning;Zhang,Hui;Xie,Zhiqin;Jin,Meilei;Li,Baoming;Yu,Lei;Jing,Naihe
• 通讯作者: Jing,Naihe

Low dose MK-801 reduces social investigation in mice.

• DOI: 10.1016/j.pbb.2008.06.002
• 发表时间: 2008-10
• 期刊: PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
• 影响因子: 3.6
• 作者: Zou, Hong;Zhang, Chenghao;Xie, Qinglian;Zhang, Manfang;Shi, Junwei;Jin, Meilei;Yu, Lei
• 通讯作者: Yu, Lei

Pairings of lever and food induce Pavlovian conditioned approach of sign-tracking and goal-tracking in C57BL/6 mice.

杠杆和食物的配对在 C57BL/6 小鼠中诱导巴甫洛夫条件性信号跟踪和目标跟踪方法。

• DOI: 10.1016/j.bbr.2011.10.021
• 发表时间: 2012
• 期刊: Behavioural brain research
• 影响因子: 2.7
• 作者: Tomie,Arthur;Lincks,Michelle;Nadarajah,SteffiD;Pohorecky,LarissaA;Yu,Lei
• 通讯作者: Yu,Lei