Cellular “trash collectors” may help Parkinson’s disease spread in the brain

Much like sticky grains of rice, abnormal alpha-synuclein clumps together, forming the Lewy bodies found in the brains and nervous systems of people with Parkinson’s. It is thought that cells’ inability to clean out these proteins causes inflammation and, ultimately, damage or death to the cell. When enough of the dopamine-producing cells in the brain are damaged or killed, Parkinson’s hallmark movement problems begin.

Although scientists have known for a while that the spread of alpha-synuclein leads to Parkinson’s disease progression, they didn’t know exactly how this happens. Using cellular models of Parkinson’s (viewed using a microscope). The new study shows that alpha-synuclein hijacks the cell’s own trash removal and transport systems to move between cells.

Here’s how it works:

• The cell recognizes alpha-synuclein fibrils (thin, wire-like extensions of the protein) as problematic and targets them for removal
• The cell sends lysosomes, which can be thought of as the cell’s trash collectors, to envelope the alpha-synuclein.
• The alpha-synuclein fibrils, in turn, promote the creation of “tunneling nanotubes,” between the affected cell and other nearby cells. Think of it like a subway tunnel connecting two stops.

Much like subway cars full of passengers, lysosomes packed with alpha-synuclein fibrils travel down the tubes and into a new cell.

Research in this area is ongoing, two recent review articles have discussed the current evidence how alpha-synuclein might spread from cell-to-cell in Parkinson’s and have highlighted this role of lysosomes and tunneling nanotubes.

• Scientific article
• News release
• Review article
• PM summary on prion-like spread