Shin Junghwan, Kim Han-Joon, Jeon Beomseok
Department of Neurology and Movement Disorder Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
J Mov Disord. 2020 Jan;13(1):11-19. doi: 10.14802/jmd.19057. Epub 2019 Dec 19.
α-Synuclein and tau deposition in the central nervous system is responsible for various parkinsonian syndromes, including Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration. Emerging evidence has suggested that pathologic α-synuclein and tau are transmitted from cell to cell and further accelerate the aggregation of pathologic proteins in neighboring cells. Furthermore, extracellular pathologic proteins have also been reported to provoke inflammatory responses that lead to neurodegeneration. Therefore, immunotherapies targeting extracellular α-synuclein and tau have been proposed as potential disease-modifying strategies. In this review, we summarize completed phase I trials and ongoing phase II trials of immunotherapies against α-synuclein and tau and further discuss concerns and hurdles to overcome in the future.
α-突触核蛋白和tau蛋白在中枢神经系统中的沉积是导致各种帕金森综合征的原因,这些综合征包括帕金森病、多系统萎缩、路易体痴呆、进行性核上性麻痹和皮质基底节变性。新出现的证据表明,病理性α-突触核蛋白和tau蛋白会在细胞间传播,并进一步加速邻近细胞中病理性蛋白质的聚集。此外,据报道细胞外病理性蛋白质也会引发导致神经变性的炎症反应。因此,针对细胞外α-突触核蛋白和tau蛋白的免疫疗法已被提出作为潜在的疾病修饰策略。在本综述中,我们总结了针对α-突触核蛋白和tau蛋白的免疫疗法已完成的I期试验和正在进行的II期试验,并进一步讨论了未来需要关注和克服的问题与障碍。