Scientists have made a major breakthrough in understanding how Parkinson’s disease develops.
Researchers have stabilised toxic protein clusters associated with the condition for long enough to be able to study them in detail for the first time.
Clusters of protein molecules known as toxic oligomers, which disrupt the membranes of healthy brain cells, are thought play a key part in Parkinson’s Disease.
The clusters have previously proved too difficult to examine, leaving experts scratching their heads as to the effect they have on Parkinson’s.
Shortly after forming the clusters either fall apart, or assemble into larger structures that are less damaging to individual cells.
For the first time, academics managed to stabilise oligomers for long enough to examine how they damage brain cell walls.
Scientists analysed the oligomer in unprecedented detail to reveal it is able to latch on to the cell wall, and a “structural core”, which then drills through into the healthy cell.
Developing a drug
Dr Giuliana Fusco, a postdoctoral researcher at St John’s College, Cambridge University, carried out much of the experimental work for the study.
She said: “Just having this information doesn’t mean that we can now go and make a drug, but obviously if we can understand why these clumps of proteins behave the way they do, we can make faster scientific progress towards treating Parkinson’s Disease.
“It means we can take a more rational approach to drug discovery.”
Toxic oligomers form at an early stage in the series of events that lead to Parkinson’s Disease, believed to begin when alpha synuclein proteins malfunction and begin to stick together, and prove lethal to neuronal function.
Once the oligomers have formed, they disperse, and allow the initial toxicity to spread to other cells.
Researchers were able to characterise different features of both toxic and non-toxic forms of oligomeric alpha synuclein oligomers using solid state nuclear magnetic resonance spectroscopy.
They then studied how these various properties influenced their interactions with sample brain cells.
The new research was led by Professor Christopher Dobson of St John’s College, Cambridge University, and Dr Alfonso De Simone from Imperial College London.
Professor Dobson said: “One of the really exciting things about this work is that not only has it been possible to define the structure of the critical pathogenic species in a neurodegenerative disorder, but we have also managed to propose a mechanism for its toxicity, providing vital clues for pursuing rational therapeutic strategies.”
The report, Structural basis of membrane disruption and cellular toxicity by a-synuclein oligomers, is published in the journal Science.