Topical themes

BREAKTHROUGH IN IDENTIFYING THE CAUSE OF PARKINSON’S DISEASE

It is possible that a single mutant protein is responsible for causing Parkinson’s disease. Researchers suspect that the protein damages the brain, which then gives incorrect ‘instructions’ to the nerves. The exceptionally successful Nanobiophysics department at the University of Twente has identified the stage in the formation of the protein at which things go seriously wrong.

It is estimated that some fifty thousand people in the Netherlands have Parkinson's disease. It is a progressive condition with increasingly severe symptoms, including tics, spasms, tremors, stiffness and (partial) paralysis. Parkinson's disease is currently incurable, its effects irreversible. Eventually, patients are likely to be completely dependent on others.

Aggregation
Parkinson's is a disease of the central nervous system, the key component of which is the brain. Until recently, the cause of the disease was completely unknown. It now seems likely that something very small plays a large part. Alpha-synucleine (also known as SCNA) is a protein found in every human brain. Sometimes, however, things go awry and the proteins aggregate (cluster together) to form insoluble 'fibrils' which destroy healthy brain cells.


parkinson

parkinson2

Schematic representation of alpha-synuclein aggregation

Nanobiophysics
The Nanobiophysics research department is led by Prof. Vinod Subramaniam. He and his team have studied the process of protein aggregation, and most importantly have identified the point at which the alpha-synucleine poses greatest risk to the brain cells. This is actually at a relatively early stage of the process. The knowledge gained may help in developing drugs which will be effective at this precise moment. If, for example, the process can be accelerated, whereby the 'danger phase' passes more quickly, it may be possible to avert the risk of serious brain damage.

Although results to date are promising, there is still much research to be done. To encourage further progress, the Netherlands Organisation for Scientific Research (NWO) awarded the Nanobiophysics department a grant of 720,000 euros (under the TOP programme) in 2009. The department also receives financial support from the IPF Foundation, a national charity which raises funds for research into Parkinson's disease.

Other mutant proteins
Mutant proteins are implicated in several other brain diseases. For example, amyloid beta (Aβ) deposits are widely thought to be the fundamental cause of Alzheimer's, the most common form of dementia. There are some 250,000 Alzheimer's patients in the Netherlands, outnumbering those with Parkinson's disease by five to one. The immense social importance of further research is clear. Prof. Subramaniam therefore hopes to expand his department's scope to examine other proteins in future.