Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep42984
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Funding
- Neuro Research Charitable Trust
- Hugh Green Foundation
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Parkinson's disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of alpha-synuclein (alpha-syn) aggregates. There is growing evidence that alpha-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 alpha-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow alpha-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain alpha-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 alpha-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 alpha-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression.
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