Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S143-7. doi: 10.1016/S1353-8020(09)70802-8.
Alpha-synuclein (alpha-syn) aggregation is central to neuropathological changes in Parkinson's disease. The aggregates spread within the central nervous system according to a very predictable pattern. A prion-like transmission of alpha-syn aggregates has been recently proposed to explain this propagation pattern. First, we review the growing evidence for such a mechanism. This process is likely to occur in three consecutive steps: (i) exit of alpha-syn template from the donor cell, (ii) entry to the recipient cell and (iii) initiation of the nucleation. In a second part, we discuss the possible underlying mechanisms for each of these steps, based on our current knowledge about how cells handle alpha-syn but also other proteins involved in neurodegenerative diseases with a prion-like propagation. Finally, we discuss which molecular species of alpha-syn (monomer, oligomer, fibril) could be the seeding-competent species and whether this seeding process could be a common mechanism in neurodegenerative diseases.
α-突触核蛋白（α-syn）聚集是帕金森病神经病理学变化的核心。这些聚集物按照一种非常可预测的模式在中枢神经系统内传播。最近提出了一种类朊病毒样的α-syn 聚集物传播机制来解释这种传播模式。首先，我们回顾了越来越多的支持这种机制的证据。这个过程可能发生在三个连续的步骤中：（i）供体细胞中α-syn 模板的排出，（ii）进入受体细胞，以及（iii）引发核形成。在第二部分中，我们根据目前对细胞如何处理α-syn 以及其他涉及具有类朊病毒样传播的神经退行性疾病的蛋白质的了解，讨论了这些步骤中的每一个步骤的可能潜在机制。最后，我们讨论了哪种α-syn 分子物种（单体、寡聚体、纤维）可能是具有成核能力的物种，以及这种成核过程是否可能是神经退行性疾病的共同机制。
