Researchers get their first look at how the toxic protein clusters associated with Parkinson’s disease disrupt the membranes of healthy brain cells. In new research, scientists have characterised the key agents involved in spreading Parkinson’s disease in the brain, and established how they ‘drill’ into the walls of healthy brain cells (neurons).
The research findings, published in the journal Science and led by researchers from Imperial College London and the University of Cambridge, will help researchers hoping to find a way to stop these agents from entering and damaging cells, leading to new and more effective treatments for the illness.
The study examined what are known as toxic oligomers – clusters of a protein called alpha synuclein that form when the individual proteins malfunction and start to bind together. The research describes how these agents bore a hole through the neuron walls, eventually causing a series of events that induce neuronal death.
Dr Alfonso De Simone, from the Department of Life Sciences at Imperial, and one of the study’s lead authors, explained: “It is a bit like if you put a piece of extremely hot metal on to a plastic surface. In a fairly short space of time it will burn a hole through the plastic.
“The oligomer does something similar when it comes into contact with the cell membrane, and this disrupts the integrity of the membrane, which is the key step in the mechanisms leading to the death of the neuron.
Until now, studying how toxic oligomers damage brain cells has been extremely difficult. The oligomers themselves are very unstable; shortly after forming they either work their way into a cell, dissolve, or bind together to form long fibres, from which yet more oligomers can break away and thus worsen the overall spread of toxicity.
In the new study, researchers were able to stabilise oligomers long enough to examine how they damage brain cell walls in unprecedented detail. They identified a specific feature of the oligomer that allows it to latch onto the cell wall, and a ‘structural core’ that then breaks through.
A structural core within a toxic oligomer allows it to ‘drill’ into the wall of a neuron (bottom).
Non-toxic oligomers that lack this feature are less penetrative (top). Illustration by Alfonso De Simone