帕金森病中的神经退行性变：环境毒素的作用

摘要(中文译文)

帕金森病（PD）是一个快速增长的全球健康挑战，预计到2040年患病率将达到1300万至1400万例。虽然老龄化和诊断意识提高部分解释了这一趋势，但越来越多的证据表明环境因素是重要诱因。本综述综合了当前关于农药、溶剂、重金属、空气污染物和感染因子等暴露因素的文献，强调其与神经退行性变的机制联系。这些因素与遗传易感性和衰老相互作用，支持“多重打击”假说，该假说认为帕金森病源于累积性损伤而非单一病因。线粒体功能障碍、氧化应激、神经炎症和蛋白质清除受损是导致多巴胺能神经元易损性的共同通路。近期研究结果强调病毒感染——尤其是SARS-CoV-2——可能是帕金森病发病机制的触发因素或放大因素，引发了对大流行后长期神经系统后遗症的担忧。除单一毒素外，暴露组学概念强调物理、化学和社会暴露在塑造疾病风险中的终生相互作用。气候相关变化，包括空气污染加剧和野火频率增加，进一步加剧了这些风险，提示帕金森病病因学具有系统性维度。理解这些复杂的相互作用对于制定预防策略、完善实验模型以及为旨在减轻环境因素对神经退行性变影响的公共卫生政策提供依据至关重要。这种多因素视角为未来针对帕金森病可干预风险因素和韧性机制的研究奠定了基础。

Abstract

Parkinson's disease (PD) is a rapidly growing global health challenge, with prevalence projected to reach 13-14 million cases by 2040. While aging and improved diagnostic awareness partly explain this trend, mounting evidence implicates environmental factors as critical contributors. This review synthesizes current literature on exposures such as pesticides, solvents, heavy metals, air pollutants, and infectious agents, emphasizing their mechanistic links to neurodegeneration. These factors interact with genetic susceptibility and aging, supporting the "multiple-hit" hypothesis, which posits that PD arises from cumulative insults rather than a single cause. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein clearance emerge as convergent pathways underlying dopaminergic vulnerability. Recent findings highlight viral infections-particularly SARS-CoV-2-as potential triggers or amplifiers of PD pathogenesis, raising concerns about long-term neurological sequelae following pandemics. Beyond individual toxins, the exposome concept underscores the lifelong interplay of physical, chemical, and social exposures in shaping disease risk. Climate-related changes, including increased air pollution and wildfire frequency, further compound these risks, suggesting a systemic dimension to PD etiology. Understanding these complex interactions is essential for developing preventive strategies, refining experimental models, and informing public health policies aimed at mitigating environmental contributions to neurodegeneration. This multifactorial perspective offers a foundation for future research targeting modifiable risk factors and resilience mechanisms in PD.

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