Project 3: Plasma Biomarkers for Parkinsonism in Welders

项目 3：焊工帕金森病的血浆生物标志物

• 批准号: 8845298
• 负责人: Jing Zhang
• 金额: $ 1.88万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-09 至 2015-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845298
• 关键词: Area; Biochemical Markers; Biological Assay; Biological Markers; Bradykinesia; Brain; Cerebrospinal Fluid; Clinical; Data; Developed Countries; Developing Countries; Development; Diagnosis; Differential Diagnosis; Disease; Environment; Environmental Exposure; Etiology; Exposure to; Functional disorder; Hand; Heavy Metals; Human; Industry; Investigation; Laboratories; Legal; Manganese; Mediating; Medical; Metal exposure; Metals; Monitor; Neurodegenerative Disorders; Parkinson Disease; Parkinsonian Disorders; Pathogenesis; Patient Monitoring; Patients; Plasma; Play; Populations at Risk; Process; Proteins; Proteomics; Risk; Risk Factors; Role; Sampling; Secondary to; Staging; Syndrome; Techniques; Tremor; Welding; base; brain tissue; design; legal implication; neuroimaging; neurotoxic; novel; prevent; therapeutic target; toxicant

Environmental exposure to metals, including manganese, is an important risk factor for the development of parkinsonism (PS) in workers of welding or related industries. However, the relevance of metal-mediated PS to idiopathic Parkinson's disease (iPD) remains to be characterized. Clinically, differential diagnosis between metal-related PS and iPD is difficult, even in the best hands. This proposal is focused on discovering plasma biochemical markers unique to welders for differential diagnosis of various PS, monitoring PS progression, and identification of the population at risk for developing disabling PS. The techniques to be utilized are state-of-the-art proteomics that are actively employed currently in our laboratory in revealing biomarkers specific to iPD in both human brain tissue and cerebrospinal fluid (CSF). Three specific aims are designed for the current proposal: 1) to differentiate PS in the plasma samples of welders from those of iPD using brain/CSF specific markers identified in iPD patients, 2) to develop plasma biomarkers unique to PS progression as well as early stages in welders using targeted and nonbiased quantitative proteomics, and 3) to confirm and validate PS plasma biomarkers in welders, which is a key process of biomarker discovery. The significance of this investigation includes: 1) identification of markers unique to PS, both in symptomatic welders and those at risk for developing PS, will help diagnose and monitor these patients as well as make it possible to remove the subjects at risk from the environment, thereby preventing them from developing PS; 2) identification of protein markers unique to PS secondary to metal exposure likely suggests novel pathogenesis and therapeutic targets for the disease process; and 3) PS markers, if identified, can be widely utilized, given that plasma-based assays can be readily implemented in a clinical setting, even in developing countries or in remote areas of developed countries.

环境暴露于包括锰在内的金属，是焊接或相关行业工人发展帕金森主义（PS）的重要危险因素。但是，金属介导的PS与特发性帕金森氏病（IPD）的相关性尚待表征。在临床上，即使在最好的手中，与金属相关的PS和IPD之间的鉴别诊断也很困难。该提案的重点是发现焊工独有的血浆生化标记，用于鉴别各种PS的鉴别，监测PS的进展以及鉴定有可能发展残疾PS的风险的人群。要使用的技术是 目前在我们的实验室中积极使用的最先进的蛋白质组学在人脑组织和脑脊液（CSF）中揭示了IPD特有的生物标志物。为当前的提案设计了三个特定目标：1）使用脑/CSF在IPD患者中确定的大脑/CSF特定标记的焊缝中的PS与IPD的血浆样本区分开生物标志物发现。 这项研究的重要性包括：1）在有症状的焊工和有发育PS的风险的PS所特有的标志物中识别标志物，将有助于诊断和监测这些患者，并使可以从环境中消除有风险的受试者，从而阻止它们开发PS； 2）鉴定蛋白质标志物是继发于金属接触的PS的蛋白质标志物，这可能表明了疾病过程的新型发病机理和治疗靶标； 3）鉴于在临床环境，即使在发展中国家或发达国家的偏远地区，基于等离子体的测定法可以很容易地实施，因此可以广泛使用PS标记。