Department of Medicine, Prisma Health Upstate, The University of South Carolina School of Medicine Greenville, Greenville, South Carolina, USA.
Distinguished Chair in Movement Disorders, Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Baylor St. Luke's Medical Center at the McNair Campus, 7200 Cambridge, 9th Floor, Suite 9A, Houston, TX, 77030-4202, USA.
CNS Drugs. 2022 Apr;36(4):327-343. doi: 10.1007/s40263-022-00903-7. Epub 2022 Feb 25.
Parkinson's disease (PD) is the second most common neurodegenerative disorder. There are several recognized pathways leading up to dopaminergic neuron loss in the substantia nigra pars compacta and other cells in the brain as a result of age-related, genetic, environmental, and other processes. Of these, the most prominent is the role played by the protein α-synuclein, which aggregates and is the primary component of Lewy bodies, the histopathological hallmark of PD. The latest disease-modifying treatment options being investigated in PD are active and passive immunization against α-synuclein. There are currently five different monoclonal antibodies investigated as passive immunization and three drugs being studied as active immunization modalities in PD. These work through different mechanisms but with a common goal-to minimize or prevent α-synuclein-driven neurotoxicity by reducing α-synuclein synthesis, increasing α-synuclein degradation, and preventing aggregation and propagation from cell to cell. These promising strategies, along with other potential therapies, may favorably alter disease progression in PD.
帕金森病（PD）是第二常见的神经退行性疾病。有几种公认的途径会导致黑质致密部多巴胺能神经元和大脑中的其他细胞丢失，这是由于年龄相关的、遗传的、环境的和其他因素导致的。在这些因素中，最为突出的是α-突触核蛋白的作用，它聚集并成为路易体的主要成分，路易体是 PD 的组织病理学标志。目前正在研究的 PD 中最新的疾病修饰治疗选择是针对α-突触核蛋白的主动和被动免疫。目前有五种不同的单克隆抗体被作为被动免疫进行研究，三种药物被作为主动免疫进行研究。这些药物通过不同的机制发挥作用，但目标是一致的——通过减少α-突触核蛋白的合成、增加α-突触核蛋白的降解，以及防止从一个细胞到另一个细胞的聚集和传播，来最小化或预防α-突触核蛋白驱动的神经毒性。这些有前途的策略，以及其他潜在的治疗方法，可能会有利于改变 PD 的疾病进展。
