Targeting alpha-synuclein via the immune system in Parkinson's disease: Current vaccine therapies.
Targeting alpha-synuclein via the immune system in Parkinson's disease: Current vaccine therapies.
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DOI：
10.1016/j.neuropharm.2021.108870
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发表时间：
2022-01-01
影响因子：
4.7
通讯作者：
Simons, Emily
中科院分区：
文献类型：
--
作者：
Fleming, Sheila M.;Davis, Ashley;Simons, Emily
帕金森病（PD）是第二大最常见的神经退行性疾病，其病理定义是突触前蛋白-突触核蛋白（aSyn）以路易小体和路易神经突的形式异常积累，以及黑质致密部中脑多巴胺能神经元的丢失。由于aSyn参与散发性和家族性PD，它已成为开发新疗法的关键靶点。异常的aSyn与多种神经元功能障碍和变性机制相关，包括炎症、线粒体功能受损、蛋白质降解系统改变和氧化应激。特别是炎症，已经成为疾病早期潜在的重要贡献者，使其成为疾病修饰和神经保护的一个有吸引力的目标。因此，针对aSyn的免疫疗法目前正在临床前和临床试验中进行研究。本综述的重点是强调asynn在神经炎症中的作用，并讨论asynn定向免疫疗法在PD临床前和临床试验中的现状。这篇文章是“帕金森病的新治疗方法”特刊的一部分。
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is defined pathologically by the abnormal accumulation of the presynaptic protein alpha-synuclein (aSyn) in the form of Lewy bodies and Lewy neurites and loss of midbrain dopaminergic neurons in the substantia nigra pars compacta. Because of aSyn’s involvement in both sporadic and familial forms of PD, it has become a key target for the development of novel therapeutics. Aberrant aSyn is associated with multiple mechanisms of neuronal dysfunction and degeneration including inflammation, impaired mitochondrial function, altered protein degradation systems, and oxidative stress. Inflammation, in particular, has emerged as a potential significant contributor early in the disease making it an attractive target for disease modification and neuroprotection. Thus, immunotherapies targeting aSyn are currently being investigated in pre-clinical and clinical trials. The focus of this review is to highlight the role of aSyn in neuroinflammation and discuss the current status of aSyn-directed immunotherapies in pre-clinical and clinical trials for PD. This article is part of the Special Issue on ‘New therapeutic approaches to Parkinson’s disease’.
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