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，经历了长时间、高强度的 职业暴露于锰(锰)的剂量。过量接触环境中的锰(Mn)会 长期以来，人们一直认为这是运动系统不良影响的原因，其临床特征类似于 帕金森综合征(PS)是帕金森病(PD)最常见的临床表现。的确有 也有证据表明，接触锰会导致认知控制、情绪和行为功能障碍。这个 拟议研究的主要目标是对锰相关疾病进行全面的临床评估。 一组具有良好特征的专业焊工的运动和认知系统神经毒性 在过去的13年里一直在学习。因此，我们将延长我们对运动系统的临床评估 毒性，并进行一系列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/行为电池将是这项研究的一个新特征。我们还将 测试已知与帕金森病相关的血浆蛋白：α突触核蛋白(SNCA)，蛋白 二甘醇(DJ1[Park7])和泛素羧基末端酯酶(UCHL1)与风险有关， 队列中PS的严重程度和进展。这项研究将在938名焊工中的500人中进行 将重新注册。这项拟议的研究将是对运动和运动障碍最全面的临床评估。 到目前为止进行的锰暴露队列中的认知神经学结果。的一个特别新奇的特点 这项拟议的研究是对可能作为临床前研究的蛋白质生物标记物测量的表征。 随后经临床确定的帕金森病预后的指标。这项研究的发现 应对制定职业性锰暴露标准产生重要影响，并最终可能 告知与锰相关的不良神经后果的疾病预防策略。

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.