帕金森氏病(PD)是一种常见的中枢神经系统退行性疾病，主要的病理改变是中脑黑质致密带内多巴胺分泌神经元的变性死亡和路易氏小体的产生。PD的药物治疗目前主要是多巴胺替代和影响多巴胺能的药物，但是这种多巴胺替代策略主要为对症治疗，而不能阻止或者缓解PD病情的进展。近来发现PD患者黑质中有明显的铁沉积，这些铁离子通过Fenton反应促进氧自由基的生成而导致的多巴胺能神经元病变，临床研究证实祛除脑内铁沉积具有神经元保护功能。如何开发一类既能有效改善疾病症状且同时能缓解或者中止PD多巴胺能神经元病变的药物是目前PD治疗的关键性问题。本研究项目是在前期研究工作的基础上，针对临床上治疗帕金森药物仅为症状性治疗，而不能缓解或者中止PD病情的进展难点, 开发一类具有多巴胺受体激动活性和祛铁能力的双重功能分子，旨在实现多靶点协同调控，以期达到症状性治疗且同时能缓解或者中止PD神经元病变的目标。

Parkinson`s disease (PD) is a progressive neurodegenerative disorder. The neuropathogenesis of PD is characterized by the degeneration of dopaminergic neurons in the midbrain substantia nigra pars compacta (SNpc) and the formation of Lewis body. Currently, the main treatment of PD focuses on the dopamine replacement strategies, which alleviate only the symptoms without affecting the course of the disease progression. Recent studies reported that significant accumulation of iron occurs in the SNpc of PD patients. The iron is thought to have a pivotal role to induce oxidative stress-dependent neurodegeneration of dopamine neurons via Fenton chemistry. Iron chelators have been shown to be neuroprotective. Therefore, beyond symptomatic relief, treatments with slowing or halting the neurodegeneration progress remain a critical unmet medical need. Based on our previous work, this project is aimed to address both the symptomatic aspect and the neurodegenerative process of disease. With this in mind, our approach is to develop such multifunctional agents, with a capacity to chelate iron along with agonist activity at dopamine D2/D3 receptors. It`s expected to discover promising candidates which not only ameliorating motor dysfunction in PD animal model, but also slowing or halting the disease progression.