Manganese-Related Motor and Cognitive System Toxicity Among Professional Welders.

摘要 美国和世界各地的数百万工人，包括专业焊工，经历了长期的，高- 职业性接触锰（Mn）。过度暴露于环境锰（Mn） 长期以来被认为是运动系统不良反应的原因，其临床特征类似于 帕金森综合征（parkinsonism，PS）是帕金森病（Parkinson disease，PD）最常见的临床表现。有 也证明锰暴露可诱导认知控制、情绪和行为的功能障碍。的 拟议研究的主要目标是对锰相关性进行全面的临床评估 在一组特征明确的专业焊工中， 已经学习了13年。因此，我们将扩展我们的运动系统的临床评估 毒性，并进行全面的认知和行为测试，并估计剂量反应 与锰暴露的关系。认知/行为组合将是这项研究的一个新特点。我们还将 检验已知与PD相关的血浆蛋白：α突触核蛋白（SNCA），蛋白质 dyglycase（DJ 1 [PARK 7]）和泛素羧基末端酯酶（UCHL 1）与风险相关， 严重程度和PS进展。这项研究将在500名（938名）焊工中进行， 将被重新注册。拟议的研究将是最全面的临床评估运动和 迄今为止进行的锰暴露队列的认知神经学结局。一个特别新颖的特点， 拟议的研究是表征蛋白质生物标志物测量， 随后临床确定的帕金森病结局的指标。这项研究的发现 应该对制定职业锰暴露标准具有重要意义，并可能最终 为锰相关不良神经学结局提供疾病预防策略。

ABSTRACT Millions of workers in the US and worldwide, including professional welders, experience prolonged, high- dose occupational exposures to manganese (Mn). Over-exposure to environmental manganese (Mn) has long been established as a cause of adverse motor system effects that have clinical features similar to parkinsonism (PS), which is the most common clinical manifestation of Parkinson disease (PD). There is also evidence that Mn exposure can induce dysfunction of cognitive control, mood, and behavior. The primary goal of the proposed investigation is to perform a comprehensive clinical assessment of Mn-related motor and cognitive system neurotoxicity among a well-characterized cohort of professional welders we have studied for the past 13 years. Accordingly, we will extend our clinical assessments of motor system toxicity and conduct a comprehensive battery of cognitive and behavioral tests, and estimate dose-response relations with Mn exposure. The cognitive/behavioral battery will be a new feature of the study. We will also test the hypothesis that plasma proteins known to be associated with PD: alpha synuclein (SNCA), protein dyglycase (DJ1 [PARK7]), and ubiquitin carboxy-terminal esterase (UCHL1), are associated with risk, severity, and progression of PS in the cohort. The study will be conducted among 500 (of 938) welders who will be re-enrolled. The proposed study will be the most comprehensive clinical assessment of motor and cognitive neurologic outcomes in an Mn-exposed cohort conducted to date. An especially novel feature of the proposed study is characterization of protein biomarker measurements that may serve as preclinical indicators of subsequent clinically determined parkinsonian outcomes. The findings from this research should have important implications for setting occupational Mn exposure standards, and may ultimately inform disease prevention strategies for Mn-related adverse neurological outcomes.