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

点击翻译按钮获取中文摘要

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.