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.

环境中接触金属（包括锰）是焊接或相关行业工人患帕金森病 (PS) 的重要风险因素。然而，金属介导的 PS 与特发性帕金森病 (iPD) 的相关性仍有待确定。在临床上，即使是最优秀的人，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特的血浆生化标记物，用于各种 PS 的鉴别诊断、监测 PS 的进展以及识别有发生致残 PS 风险的人群。要利用的技术是 我们的实验室目前积极采用最先进的蛋白质组学来揭示人脑组织和脑脊液 (CSF) 中 iPD 特异的生物标志物。当前提案设计了三个具体目标：1）使用 iPD 患者中识别的大脑/CSF 特异性标记物区分焊工血浆样本中的 PS 和 iPD 样本，2）开发 PS 进展以及早期独特的血浆生物标记物使用靶向和无偏定量蛋白质组学在焊工中进行阶段，以及 3) 确认和验证焊工中的 PS 血浆生物标志物，这是生物标志物发现的关键过程。 这项调查的意义包括：1) 鉴定出 PS 特有的标记，无论是在有症状的焊工还是有发生 PS 风险的焊工中，都将有助于诊断和监测这些患者，并有可能将处于危险中的受试者从环境中移除，从而阻止他们发展PS； 2) 继发于金属暴露的 PS 特有的蛋白质标记的鉴定可能提示疾病过程的新发病机制和治疗靶点； 3) PS标记如果被鉴定，可以被广泛使用，因为基于血浆的检测可以很容易地在临床环境中实施，甚至在发展中国家或发达国家的偏远地区。