AD/PD 2022 | How does α-synuclein propagate from cell to cell?

So in terms of our latest developments about α-synuclein propagation, we’ve learned that it’s probably not just one mechanism that cells use to get rid of the protein or to release the protein and then to take it up. There was work presented here on the transmission of α-synuclein via these very tiny structures called tunneling nanotubes. They are tubes formed by an actin that can transport, for example, lysosomal vesicles, mitochondria. And it seems that α-synuclein can travel between one cell to the other within these lysosomal vesicles that are passed between cells.

It’s done, so far, only in models in laboratory, but it’s one possibility. Then, of course, there’s other possibilities. We know more and more about possible proteins that exist at the membranes of cells that connect as receptors to then help α-synuclein enter the cells to sort it to the lysosomal pathway from where it can be released and then exposed to endogenous protein in the recipient cell and then trigger the aggregation of the protein. So we know more about the molecular details. We know about trafficking proteins that play a role in these sorting steps inside the cell, and so I think we’re making good progress, but there’s still a lot to do.