Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.
Nat Rev Drug Discov. 2011 May;10(5):377-93. doi: 10.1038/nrd3430.
The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.
运动迟缓、僵直和静止性震颤。尽管目前可用的多巴胺替代策略可以改善这些症状，但仍需要改进治疗这些症状的现有策略，同时需要减轻疾病的非运动症状。此外，提供神经保护和/或疾病修饰作用的治疗方法仍然是一个迫切未满足的临床需求。本综述描述了目前正在评估以实现这些治疗目标的最有前途的生物靶点和治疗剂。进展将依赖于对导致帕金森病的遗传突变或易感性因素的理解、更好地在临床前动物模型和临床研究之间进行转化，以及改进未来临床试验的设计。
