Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Malaysia.
Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Italy.
Drug Discov Today. 2019 Sep;24(9):1769-1783. doi: 10.1016/j.drudis.2019.05.003. Epub 2019 May 16.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed.
帕金森病(PD)是一种神经退行性疾病,其特征是多巴胺能神经元退化。震颤、僵硬、运动迟缓以及姿势不稳等运动特征是 PD 的常见特征。目前的治疗选择仅能提供对症缓解,但无法逆转疾病进展。由于 PD 的多因素性质,传统的单一靶点治疗方法可能并不总是能产生预期的效果。因此,已经提出了多靶点策略,以同时针对 PD 发展过程中涉及的多种蛋白质。本文综述了 PD 的发病机制和当前的药物治疗方法。此外,还讨论了已在临床试验中用于治疗 PD 的多靶点方法的原理和实例。