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

摘要 美国和世界各地数以百万计的工人，包括专业焊工，都经历着长期、高强度的工作。 职业接触锰 (Mn) 的剂量。过度接触环境锰（Mn）已 长期以来被认为是运动系统不良反应的一个原因，其临床特征类似于 帕金森病（PS）是帕金森病（PD）最常见的临床表现。有 还有证据表明，锰暴露会导致认知控制、情绪和行为功能障碍。的 拟议研究的主要目标是对锰相关的疾病进行全面的临床评估 我们对一组特征明确的专业焊工的运动和认知系统神经毒性进行了研究 已经学习了13年了。因此，我们将扩展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/行为电池将是该研究的一个新特点。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 (DJ1 [PARK7]) 和泛素羧基末端酯酶 (UCHL1) 与风险相关， 队列中 PS 的严重程度和进展。该研究将在 500 名（共 938 名）焊工中进行，他们 将重新注册。拟议的研究将是对运动和运动最全面的临床评估 迄今为止进行的锰暴露队列的认知神经学结果。一个特别新颖的特点是 拟议的研究是蛋白质生物标志物测量的表征，可作为临床前研究 随后临床确定的帕金森病结果的指标。这项研究的结果 对制定职业锰暴露标准具有重要意义，并可能最终 为与锰相关的不良神经系统结果的疾病预防策略提供信息。

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.