Single protein causes Parkinson’s disease and Multiple System Atrophy

Parkinson's disease is induced by alpha-synuclein strains shaped like 'cylinders' (c) Shutterstock

_{10 June 2015}                                                                

Several neurodegenerative disorders are caused by aggregates of a single protein known as alpha-synuclein. In collaboration with CNRS and the University of Antwerp, KU Leuven neurobiologists have discovered that the shape of these aggregates – ‘cylinders’ or ‘ribbons’ – determines whether a patient develops Parkinson’s disease or Multiple System Atrophy, respectively.

Typical of neurodegenerative disorders is the disrupted 

communication between brain cells together with a loss of 

cells in specific brain regions. For some brain diseases this phenomenon is linked to a

 protein known as alpha-synuclein. The exact function of this protein remains unclear, but it 

may play a role in the communication between brain cells. However, in the case of specific 

diseases, including Parkinson’s disease, Multiple System Atrophy (MSA), and dementia 

with Lewy bodies (DLB), this protein forms aggregates that cause neurodegeneration.

“When alpha-synuclein aggregates accumulate within a brain cell, they interfere with the 

normal functioning of the cell. The protein aggregates disrupt the communication between 

brain cells, resulting in cell death. Up to now, nobody understood how aggregates of this

 single protein could induce different pathologies,” says Professor Veerle Baekelandt from 

the Research Group for Neurobiology and Gene Therapy.

“You could compare it to the construction of a house,” doctoral researcher Wouter 

Peelaerts explains. “With the same building blocks – in this case the alpha-synuclein 

protein – you can create many different structures. In 2013, Professor Ronald Melki and his 

colleagues from CNRS isolated several forms of fibres called ‘strains’. The two most

 important strains were cylinder-shaped fibres reminiscent of spaghetti and broad ribbons 

that resemble linguini. We injected these fibres separately into the brain and blood stream of

 rats. We noticed that the rats developed different symptoms: while the ‘cylinders’ induced 

Parkinson’s disease, the ‘ribbons’ caused MSA symptoms.” This clearly demonstrates that 

distinct diseases result from alpha-synuclein fibres that are structurally different.

“We are gaining more insight into the differences between the diseases," Baekelandt 

concludes. "But we suspect that more fibres with different shapes and effects are waiting to 

be discovered, apart from the two that we examined in this study. In any case, our findings 

open up possibilities for the development of new treatments. A drug that counteracts the 

development of aggregates could be used to treat a whole range of brain diseases.”

http://www.kuleuven.be/english/news/2015/single-protein-causes-parkinsons-disease-and-multiple-system-atrophy