Abstract：
Parkinson\'s disease (PD) is a debilitating neurodegenerative disease affecting millions of individuals worldwide. Hallmark features of PD pathology are the formation of Lewy bodies in neuromelanin-containing dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc), and the subsequent irreversible death of these neurons. Although genetic risk factors have been identified, around 90 % of PD cases are sporadic and likely caused by environmental exposures and gene-environment interaction. Mechanistic studies have identified a variety of chemical PD risk factors. PD neuropathology occurs throughout the brain and peripheral nervous system, but it is the loss of DAergic neurons in the SNpc that produce many of the cardinal motor symptoms. Toxicology studies have found specifically the DAergic neuron population of the SNpc exhibit heightened sensitivity to highly variable chemical insults (both in terms of chemical structure and mechanism of neurotoxic action). Thus, it has become clear that the inherent neurobiology of nigral DAergic neurons likely underlies much of this neurotoxic response to broad insults. This review focuses on inherent neurobiology of nigral DAergic neurons and how such neurobiology impacts the primary mechanism of neurotoxicity. While interactions with a variety of other cell types are important in disease pathogenesis, understanding how inherent DAergic biology contributes to selective sensitivity and primary mechanisms of neurotoxicity is critical to advancing the field. Specifically, key biological features of DAergic neurons that increase neurotoxicant susceptibility.
摘要：
帕金森病（PD）是一种使人衰弱的神经退行性疾病，影响着全世界数百万人。PD病理学的标志特征是在黑质致密部（SNpc）的含神经黑色素的多巴胺能神经元中形成路易体，以及随后这些神经元的不可逆死亡。尽管已经确定了遗传风险因素，大约90％的PD病例是零星的，可能是由环境暴露和基因-环境相互作用引起的。机理研究已经确定了多种化学PD危险因素。PD神经病理学发生在整个大脑和周围神经系统，但是SNpc中多巴胺神经元的丢失会产生许多主要的运动症状。毒理学研究特别发现，SNpc的多巴胺能神经元群体对高度可变的化学损伤（在化学结构和神经毒性作用机制方面）表现出更高的敏感性。因此，很明显，黑质多巴胺神经元的固有神经生物学可能是这种对广泛侮辱的神经毒性反应的基础。这篇综述着重于黑质多巴胺能神经元的固有神经生物学以及这种神经生物学如何影响神经毒性的主要机制。虽然与多种其他细胞类型的相互作用在疾病发病机理中很重要，了解固有的多巴胺能生物学如何有助于神经毒性的选择性敏感性和主要机制对于推进该领域至关重要。具体来说,多巴胺能神经元增加神经毒性易感性的关键生物学特征。
