Parkinson’s disease (PD) is a movement disorder associated with severe loss of mainly dopaminergic neurons in the substantia nigra. Pathological hallmarks include Lewy bodies, and loss of neuromelanin, due to degeneration of neuromelanin-containing dopaminergic neurons. Despite being described over 200 years ago, the etiology of PD remains unknown. Here, we highlight the roles of reactive oxygen species (ROS), iron, alpha synuclein (α-syn) and neuromelanin in a toxic feedback loop culminating in neuronal death and spread of the disease. Dopaminergic neurons are particularly vulnerable due to decreased antioxidant concentration with aging, constant exposure to ROS and presence of neurotoxic compounds (e.g. ortho-quinones). ROS and iron increase each other’s levels, creating a state of oxidative stress. α-Syn aggregation is influenced by ROS and iron but also increases ROS and iron via its induced mitochondrial dysfunction and ferric-reductase activity. Neuromelanin’s binding affinity is affected by increased ROS and iron. Furthermore, during neuronal death, neuromelanin is degraded in the extracellular space, releasing its bound toxins. This cycle of events continues to neighboring neurons in the form of a toxic loop, causing PD pathology. The increase in ROS and iron may be an important target for therapies to disrupt this toxic loop, and therefore diets rich in certain ‘nutraceuticals’ may be beneficial. Turmeric is an attractive candidate, as it is known to have anti-oxidant and iron chelating properties. More studies are needed to test this theory and if validated, this would be a step towards development of lifestyle-based therapeutic modalities to complement existing PD treatments.

帕金森病 (PD) 是一种运动障碍，与黑质中主要多巴胺能神经元的严重丧失有关。病理特征包括路易体和由于含有神经黑色素的多巴胺能神经元的退化而导致的神经黑色素损失。尽管在 200 多年前已被描述，但 PD 的病因仍然未知。在这里，我们强调了活性氧 (ROS)、铁、α-突触核蛋白 (α-syn) 和神经黑色素在最终导致神经元死亡和疾病传播的毒性反馈回路中的作用。多巴胺能神经元特别脆弱，因为随着衰老、持续暴露于 ROS 和神经毒性化合物（例如邻醌）的存在而降低抗氧化剂浓度。ROS 和铁会增加彼此的水平，从而产生氧化应激状态。α-Syn 聚集受 ROS 和铁的影响，但也通过其诱导的线粒体功能障碍和铁还原酶活性增加 ROS 和铁。神经黑色素的结合亲和力受增加的 ROS 和铁的影响。此外，在神经元死亡期间，神经黑色素在细胞外空间降解，释放其结合的毒素。这种事件循环以有毒循环的形式持续到邻近的神经元，导致 PD 病理。活性氧和铁的增加可能是治疗破坏这种毒性循环的重要目标，因此富含某些“营养保健品”的饮食可能是有益的。姜黄是一个有吸引力的候选者，因为它具有抗氧化和铁螯合特性。需要更多的研究来检验这一理论，如果得到验证，