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?-synuclein transfer through tunneling nanotubes occurs in SH-SY5Y cells and primary brain pericytes from Parkinson?s disease patients #MMPMID28230073
Dieriks BV; Park TIH; Fourie C; Faull RLM; Dragunow M; Curtis MA
Sci Rep 2017[]; 7 (ä): ä PMID28230073show ga
Parkinson?s disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of ?-synuclein (?-syn) aggregates. There is growing evidence that ?-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for ?-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow ?-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain ?-syn precipitates like those seen in neurons. Exchange through TNTs was rapid, but dependent on the size of the protein. Proteins were able to spread throughout a network of cells connected by TNTs. Transfer through TNTs was not restricted to ?-syn; fluorescent control proteins and labeled membrane were also exchanged through TNTs. Most importantly the formation of TNTs and transfer continued during mitosis. Together, our results provide a detailed description of TNTs in SH-SY5Y cells and human brain PD pericytes, demonstrating their role in ?-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression.