Analyses on the mode of proteolysis and aggregation of synphilin-1 that constitutes the core of Lewy bodies

疾病特异性蛋白质的蛋白水解过程中的损伤被认为是神经元包涵体形成和随后神经元细胞死亡的原因。在帕金森病中，Synphilin-1是路易体的成分之一，其在病理上表征帕金森病。我们假设胞内囊泡运输的扰动是导致神经元包涵体形成的根本原因，并阐明ESCRT（内体转运所需的分选复合物）途径与路易体形成有关。我们还证明Siah-1对Synphilin-1的泛素化是将Synphilin-1募集到ESCRT通路的信号。

Impairments in the proteolytic process of disease-specific proteins have been assumed to be the cause of the formation of neuronal inclusions and subsequent neuronal cell death. In Parkinson' s disease, Synphilin-1 is one of the constituents of Lewy bodies that characterize Parkinson' s disease pathologically. We hypothesized that the perturbation of intracellular vesicle trafficking is the underlying cause which leads to the formation of neuronal inclusion, and elucidated that ESCRT(endosomal sorting complex required for transport) pathway is implicated in the Lewy bodies formation. We also demonstrated that ubiquitination of Synphilin-1 by Siah-1 is a signal that recruit Synphilin-1 to ESCRT pathway.