{alpha}-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease

In this study, we examined the role of the endosomal sorting complex required for transport (ESCRT) pathway on the propagation of α-syn. α-syn, which is transported via the ESCRT pathway through multivesicular bodies for degradation, can also target the degradation of the ESCRT protein-charged multivesicular body protein (CHMP2B), thus generating a roadblock of endocytosed α-syn. Disruption of the ESCRT transport system also resulted in increased exocytosis of α-syn thus potentially increasing cell-to-cell propagation of synuclein. Conversely, delivery of a lentiviral vector overexpressing CHMP2B rescued the neurodegeneration in α-syn transgenic mice. Better understanding of the mechanisms of intracellular trafficking of α-syn might be important for understanding the pathogenesis and developing new treatments for synucleinopathies.

Source: Human Molecular Genetics - February 23, 2016 Category: Genetics & Stem Cells Authors: Spencer, B., Kim, C., Gonzalez, T., Bisquertt, A., Patrick, C., Rockenstein, E., Adame, A., Lee, S.-J., Desplats, P., Masliah, E. Tags: ARTICLES Source Type: research