Abstract：
Parkinson\'s Disease (PD) is the most common neurodegenerative disorder after Alzheimer\'s Disease and is clinically expressed by movement disorders, such as tremor, bradykinesia, and rigidity. It occurs mainly in the extrapyramidal system of the brain and is characterized by dopaminergic neuron degeneration. L-DOPA, dopaminergic agonists, anticholinergic drugs, and MAO-B inhibitors are currently used as therapeutic agents against PD, however, they have only symptomatic efficacy, mainly due to the complex pathophysiology of the disease. This review summarizes the main aspects of PD pathology, as well as, discusses the most important biochemical dysfunctions during PD, and presents novel multi-targeting compounds, which have been tested for their activity against various targets related to PD. This review selects various research articles from main databases concerning multi-targeting compounds against PD. Molecules targeting more than one biochemical pathway involved in PD, expected to be more effective than the current treatment options, are discussed. A great number of research groups have designed novel compounds following the multi-targeting drug approach. They include structures combining antioxidant, antiinflammatory, and metal-chelating properties. These compounds could be proven useful for effective multi-targeted PD treatment. Multi-targeting drugs could be a useful tool for the design of effective antiparkinson agents. Their efficacy towards various targets implicated in PD could be the key to the radical treatment of this neurodegenerative disorder.
摘要：
帕金森病（PD）是阿尔茨海默病之后最常见的神经退行性疾病，临床上表现为运动障碍，比如震颤，运动迟缓,和刚性。它主要发生在大脑的锥体外系，以多巴胺能神经元变性为特征。L-DOPA,多巴胺能激动剂，抗胆碱能药物，MAO-B抑制剂目前被用作PD的治疗药物，然而,它们只有症状疗效，主要是由于疾病的复杂病理生理学。这篇综述总结了PD病理学的主要方面，还有,讨论了PD期间最重要的生化功能障碍，并提出了新的多靶向化合物，已针对与PD相关的各种靶标进行了活性测试。这篇综述从主要数据库中选择了有关抗PD的多靶向化合物的各种研究文章。靶向多个参与PD的生化途径的分子，预计比目前的治疗方案更有效，正在讨论。许多研究小组按照多靶向药物方法设计了新型化合物。它们包括结合抗氧化剂的结构，抗炎,和金属螯合性能。这些化合物可被证明可用于有效的多靶向PD治疗。多靶向药物可能是设计有效的抗帕金森病药物的有用工具。它们对涉及PD的各种靶标的功效可能是根治性治疗这种神经退行性疾病的关键。
