Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval, Québec, QC, Canada.
CERVO Brain Research Centre, 2601, chemin de la Canardière, Québec, QC, Canada.
J Parkinsons Dis. 2021;11(1):71-92. doi: 10.3233/JPD-202221.
Parkinson's disease is a neurodegenerative disorder mainly characterized by the degeneration of dopaminergic neurons in the substantia nigra. Degenerating neurons contain abnormal aggregates called Lewy bodies, that are predominantly composed of the misfolded and/or mutated alpha-synuclein protein. Post-translational modifications, cellular stress, inflammation and gene mutations are thought to trigger its pathological misfolding and aggregation. With alpha-synuclein pathology being strongly associated with dopaminergic neuronal toxicity, strategies aimed to reduce its burden are expected to be beneficial in slowing disease progression. Moreover, multiple sources of evidence suggest a cell-to-cell transmission of pathological alpha-synuclein in a prion-like manner. Therefore, antibodies targeting extra- or intracellular alpha-synuclein could be efficient in limiting the aggregation and transmission. Several active and passive immunization strategies have been explored to target alpha-synuclein. Here, we summarize immunotherapeutic approaches that were tested in pre-clinical or clinical studies in the last two decades in an attempt to treat Parkinson's disease.
帕金森病是一种神经退行性疾病，主要特征是黑质中多巴胺能神经元的退化。退化的神经元包含异常聚集物，称为路易体，主要由错误折叠和/或突变的α-突触核蛋白组成。翻译后修饰、细胞应激、炎症和基因突变被认为会引发其病理性错误折叠和聚集。由于α-突触核蛋白病理学与多巴胺能神经元毒性密切相关，因此旨在减轻其负担的策略有望减缓疾病进展。此外，多项证据表明，病理性α-突触核蛋白以类朊病毒的方式在细胞间传播。因此，针对细胞外或细胞内α-突触核蛋白的抗体可能在限制聚集和传播方面非常有效。已经探索了几种主动和被动免疫策略来靶向α-突触核蛋白。在这里，我们总结了过去二十年在临床前或临床试验中测试过的针对帕金森病的免疫治疗方法。
