The UCLA Udall Parkinson Disease Center of Excellence

加州大学洛杉矶分校尤德尔帕金森病卓越中心

• 批准号: 8322208
• 负责人: MARIE-FRANCOISE S CHESSELET
• 金额: $ 11.24万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322208
• 关键词: Award; Basic Science; Behavioral; Cell Death; Cell model; Cells; Clinical; Clinical Data; Clinical Research; Cognitive; Comorbidity; Complement; Coupled; Data; Development; Diagnosis; Disease; Experimental Models; Functional disorder; Future; Genetic; Genetic Materials; Goals; Longitudinal Studies; Modeling; Motor; Mus; Mutation; Nerve Degeneration; Neurons; Parkinson Disease; Patient Care; Patients; Phenotype; Process; Quality-of-Life Assessment; Symptoms; Technology; Translations; Validation; Work; base; disease phenotype; disease-causing mutation; health related quality of life; improved; mouse model; multidisciplinary; neuropathology; neurotransmitter release; new therapeutic target; novel; patient oriented; patient oriented research; patient population; synaptic function; therapeutic development; tool

New evidence indicates that distinct mutations cause familial Parkinson's disease (PD) by mechanisms that may also operate in sporadic PD. These new data point to the importance of cell dysfunction preceding cell death and to the involvement of non-dopaminergic neurons in the disease. Accordingly, identifying mechanisms of cellular dysfunction that are common to multiple causes of PD may offer new therapeutic targets to halt or reverse the course of the disease. This renewal application for the UCLA UDALL Parkinson Disease Center of Excellence focuses on studies of progression of dysfunction, in complementary models expressing PD-causing mutations, and in a well characterized patient population. The center consists of 5 projects supported by an administrative core and a mouse genetics core. In the first three projects we propose to continue coordinated multidisciplinary work supported by the current award to characterize the progression of motor and non-motor behavioral anomalies and neuropathology (project 1), anomalies of neurotransmitter release (project 2) and of synaptic function (project 3) in genetic mouse models of PD, including novel models based on BAG technology. These projects will be complemented by the addition of cellular models (project 4) to analyze the mechanisms of cellular dysfunction leading to the phenotypes observed in the mouse. Studying progression of dysfunction will also be the focus of the new patient oriented component of the Center. In this project (project 5), we will conduct clinical longitudinal studies of disease phenotype after diagnosis, including psychiatric and cognitive co-morbidities. This will be coupled to the development and validation of an improved health-related quality of life assessment tool. These patient oriented studies will provide crucial clinical data for future analyses of genetic material from the same patients and for the translation of our basic research efforts into improved patient care. To identify the cellular alterations leading to neurodegeneration in PD, the UCLA UDALL Parkinson Disease Center of Excellence will focus on early manifestations of the disease occurring before the onset of motor symptoms and their progression. Integrating experimental models and clinical studies, the goal of our center is to understand the mechanisms of these cellular dysfunctions in order to spur the development of therapeutic strategies able to stop the disease process.

新的证据表明，不同的突变引起家族性帕金森病（PD）的机制也可能在散发性帕金森病中起作用。这些新的数据指出了细胞死亡前细胞功能障碍的重要性，以及非多巴胺能神经元在疾病中的参与。因此，识别多种PD病因中常见的细胞功能障碍机制可能提供新的治疗靶点，以阻止或逆转PD的病程。加州大学洛杉矶分校UDALL帕金森病卓越中心的更新申请侧重于功能障碍进展的研究，在表达pd引起突变的互补模型中，以及在具有良好特征的患者群体中。该中心由5个项目组成，由一个行政核心和一个小鼠遗传学核心支持。在前三个项目中，我们建议在当前奖项的支持下继续协调多学科工作，以表征PD遗传小鼠模型中运动和非运动行为异常和神经病理学（项目1），神经递质释放异常（项目2）和突触功能异常（项目3）的进展，包括基于BAG技术的新模型。这些项目将通过增加细胞模型（项目4）来补充，以分析导致小鼠观察到的表型的细胞功能障碍机制。研究功能障碍的进展也将是该中心以患者为导向的新组成部分的重点。在本项目（项目5）中，我们将对诊断后的疾病表型进行临床纵向研究，包括精神和认知合并症。这将与开发和验证改进的与健康有关的生活质量评估工具相结合。这些以患者为导向的研究将为未来对同一患者遗传物质的分析提供关键的临床数据，并将我们的基础研究成果转化为改善患者护理。

项目成果

Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease.

• DOI: 10.1097/ede.0b013e3181c15ec6
• 发表时间: 2010-01
• 期刊: Epidemiology (Cambridge, Mass.)
• 作者: Manthripragada AD;Costello S;Cockburn MG;Bronstein JM;Ritz B
• 通讯作者: Ritz B

The Promise of Mendelian Randomization in Parkinson's Disease: Has the Smoke Cleared Yet for Smoking and Parkinson's Disease Risk?

• DOI: 10.3233/jpd-223188
• 发表时间: 2022
• 期刊: JOURNAL OF PARKINSONS DISEASE
• 影响因子: 5.2
• 作者: Ritz, Beate R.;Kusters, Cynthia D. J.
• 通讯作者: Kusters, Cynthia D. J.

Effect of neurturin on multipotent cells isolated from the adult skeletal muscle.

神经营养因子对从成人骨骼肌中分离的多能细胞的影响。

• DOI: 10.1016/j.bbrc.2005.04.104
• 发表时间: 2005
• 期刊: Biochemical and biophysical research communications.
• 作者: Vourc'h,Patrick;Lacar,Benjamin;Mignon,Laurence;Lucas,PaulA;Young,HenryE;Chesselet,Marie-Francoise
• 通讯作者: Chesselet,Marie-Francoise

Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.

• DOI: 10.1016/j.nbd.2014.05.012
• 发表时间: 2014-09
• 期刊: Neurobiology of disease
• 影响因子: 6.1
• 作者: Richter F;Gao F;Medvedeva V;Lee P;Bove N;Fleming SM;Michaud M;Lemesre V;Patassini S;De La Rosa K;Mulligan CK;Sioshansi PC;Zhu C;Coppola G;Bordet T;Pruss RM;Chesselet MF
• 通讯作者: Chesselet MF

Gout and the risk of Parkinson's disease in Denmark.

丹麦的痛风和帕金森病的风险。

• DOI: 10.1007/s10654-013-9791-1
• 发表时间: 2013
• 期刊: European journal of epidemiology
• 影响因子: 13.6
• 作者: Schernhammer,Eva;Qiu,Jiaheng;Wermuth,Lene;Lassen,ChristinaFunch;Friis,Soren;Ritz,Beate
• 通讯作者: Ritz,Beate