Abstract：
Parkinson\'s disease (PD) has two main pathological hallmarks, the loss of nigral dopamine neurons and the proteinaceous aggregations of ⍺-synuclein (⍺Syn) in neuronal Lewy pathology. These two co-existing features suggest a causative association between ⍺Syn aggregation and the underpinning mechanism of neuronal degeneration in PD. Both increased levels and post-translational modifications of ⍺Syn can contribute to the formation of pathological aggregations of ⍺Syn in neurons. Recent studies have shown that the protein is also expressed by multiple types of non-neuronal cells in the brain and peripheral tissues, suggesting additional roles of the protein and potential diversity in non-neuronal pathogenic triggers. It is important to determine (1) the threshold levels triggering ⍺Syn to convert from a biological to a pathologic form in different brain cells in PD; (2) the dominant form of pathologic ⍺Syn and the associated post-translational modification of the protein in each cell type involved in PD; and (3) the cell type associated biological processes impacted by pathologic ⍺Syn in PD. This review integrates these aspects and speculates on potential pathological mechanisms and their impact on neuronal and non-neuronal ⍺Syn in the brains of patients with PD.
摘要：
帕金森病（PD）有两个主要的病理标志，神经元路易病理中黑色多巴胺神经元的丢失和synuclein（Syn）的蛋白质聚集。这两个共存的特征表明，在PD中，Syn聚集与神经元变性的基础机制之间存在因果关系。增加的水平和翻译后修饰都可以促进神经元中Syn的病理性聚集的形成。最近的研究表明，该蛋白也由大脑和外周组织中多种类型的非神经元细胞表达，提示蛋白质在非神经元致病触发因素中的其他作用和潜在的多样性。重要的是要确定（1）在PD中不同脑细胞中触发小鼠Syn从生物学形式转变为病理学形式的阈值水平；（2）与PD有关的每种细胞类型中的病理蛋白Syn的主要形式和相关的翻译后修饰；（3）与PD中病理Syn影响的细胞类型相关的生物过程。这篇综述整合了这些方面，并推测了潜在的病理机制及其对PD患者大脑中神经元和非神经元的影响。
