Endotoxin Exposure and Risk of Parkinsonism

项目摘要 帕金森综合征（PS）是一种使人衰弱的神经退行性疾病，影响数百万人 国际吧原发性（特发性）PS的原因在很大程度上是未知的，尽管有 越来越多的实验和流行病学证据表明，环境毒物 病因作用内毒素（脂多糖）是细菌外膜的一种成分， 革兰氏阴性菌细胞壁，细菌裂解时释放。人类接触 内毒素存在于许多环境中，在棉花中发现的内毒素水平特别高 纺织制造业，这是本研究的重点。值得注意的是 内毒素已被确立为诱导选择性死亡的模型实验剂， 多巴胺能神经元在体外和体内。尽管有令人信服的实验支持， 内毒素在PS中可能的致病作用，以前没有流行病学研究 已经明确测试了这种关联。因此，我们建议进行一项 纺织女工PS的流行病学研究 中国上海，我们以前研究过癌症的危险因素。我们之前的研究 已经产生了内毒素累积剂量的定量估计。我们会进行 标准化的神经系统检查，以确定红衣主教的患病率和严重程度 600名曾在棉花厂工作的退休妇女帕金森综合征的体征和症状 暴露于内毒素的纺织厂和年龄匹配的非暴露组 由300名从未在棉纺厂或纺织厂工作过的退休纺织女工组成， 可能接触内毒素的工作我们还将对这些患者进行为期3年的临床随访， 在项目第1年和第2年确定的PS病例，以确定疾病进展。我们 分析将产生内毒素暴露关系的定量剂量反应趋势 PS风险、严重程度和进展，根据年龄调整潜在混杂因素， 吸烟、生育史和其他职业暴露。这个项目的发现 有很大的希望，以进一步阐明神经炎症在人类发病机制中的作用， 帕金森综合征，这将最终是重要的预防这种疾病。

Project Summary Parkinsonism (PS) is a debilitating neurodegenerative disorder that affects millions of people worldwide. The causes of primary (idiopathic) PS are largely unknown, although there is growing experimental and epidemiologic evidence that environmental toxicants play important etiologic roles. Endotoxin (lipopolysaccharide) is a component of the outer membranes of Gram-negative bacteria cell walls that is released when bacteria lyse. Human exposure to endotoxin occurs in numerous environmental settings, with especially high levels found in cotton textile manufacturing, which is the focus of this proposed research. It is noteworthy that endotoxin has been established as a model experimental agent that induces selective death of dopaminergic neurons in vitro and in vivo. Despite convincing experimental support for a plausible pathogenic role of endotoxin in PS, there have been no previous epidemiologic studies that have explicitly tested this association. Accordingly, we are proposing to conduct an epidemiological study of PS among a well-characterized cohort of women textile workers in Shanghai, China that we have studied previously for cancer risk factors. Our previous research has generated quantitative estimates of cumulative doses of endotoxin. We will conduct standardized neurological examinations to determine the prevalence and severity of the cardinal signs and symptoms of parkinsonism among 600 retired women previously employed in cotton textile factories who were exposed to endotoxin and an age-matched non-exposed group composed of 300 retired women textile workers who had never worked in cotton factories or in jobs with potential endotoxin exposure. We will also perform a 3-year clinical follow-up among PS cases identified in years 1 and 2 of the project to determine disease progression. Our analyses will generate quantitative dose-response trends for relations of endotoxin exposure with PS risk, severity, and progression that are adjusted for potential confounding by age, smoking, reproductive history, and other occupational exposures. The findings from this project have great promise to clarify further the role of neuroinflammation in the pathogenesis of human parkinsonism, which will ultimately be important for prevention of this disorder.