Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 7200 Cambridge, Suite 9A, Houston, TX, 77030-4202, USA.
Drugs. 2019 Jun;79(8):797-810. doi: 10.1007/s40265-019-01104-1.
Parkinson's disease (PD), the second most common neurodegenerative movement disorder, is characterized by progressive motor and non-motor symptoms [1]. Despite treatment with pharmacologic and surgical therapies, the disease will continue to relentlessly advance. Hence, there is a great deal of interest in potential disease-modifying therapies with the hope that the neurodegenerative process can be slowed or halted. The purpose of this review is to highlight the role toxic α-synuclein (α-syn) plays in PD pathogenesis and critically review the relevant literature about therapeutic modalities targeting α-syn. Toxic α-syn plays a key role in PD pathogenesis, disrupting important cellular functions, and, thus, targeting α-syn is a reasonable disease-modifying strategy. Current approaches under investigation include decreasing α-syn production with RNA interference (RNAi), inhibiting α-syn aggregation, promoting intracellular degradation of α-syn aggregates (via enhancing autophagy and enhancing lysosomal degradation), and promoting extracellular degradation of α-syn via active and passive immunization.
帕金森病（PD）是第二常见的神经退行性运动障碍，其特征是进行性运动和非运动症状[1]。尽管采用了药物和手术治疗，但疾病仍会持续进展。因此，人们对潜在的疾病修饰疗法非常感兴趣，希望能够减缓或阻止神经退行性过程。本综述的目的是强调毒性α-突触核蛋白（α-syn）在 PD 发病机制中的作用，并批判性地回顾关于靶向α-syn 的治疗方式的相关文献。毒性α-syn 在 PD 发病机制中起关键作用，破坏重要的细胞功能，因此，靶向α-syn 是一种合理的疾病修饰策略。目前正在研究的方法包括使用 RNA 干扰（RNAi）减少α-syn 的产生、抑制α-syn 聚集、促进细胞内α-syn 聚集的降解（通过增强自噬和增强溶酶体降解）以及通过主动和被动免疫促进α-syn 的细胞外降解。
