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Parkinson Protein α-Synuclein Binds Surprisingly Strong with Membrane (article in PLoS ONE by LION researchers Pravin Kumar and Martina Huber and colleagues)

[07-12-2015]

(By LION/EA)
Α-synuclein, a protein associated with Parkinson’s disease, proves to bind with membranes in a surprisingly efficient way. It confirms the scientists’ suspicion of the leading role of that protein in the transmission of neurotransmitters between nerve cells in the brain.

Physicists of the universities of Leiden and Twente studied the binding process of α-synuclein with small vesicles. During the research, these played the part of specific vesicles which attach to the brain membrane and transfer neurotransmitters. First author Pravin Kumar and his colleagues used the Leiden developed method of keeping track of the binding process through electron spins. Their research is published in PLoS ONE

Parkinson
Parksinson’s disease is the second most prevalent neurodegenerative disorder. Within the brain of a Parkinson patient, something goes wrong during the transport of neurotransmitters, which provide the communication between nerve cells. But it is still unknown when and where exactly the error occurs. However, scientist have already discovered that proteins accumulate in the brain, and α-synuclein is notably abundant there. The suspiciously dominant presence of this protein was cause for group leader Dr. Martina Huber to study its behavior.

Tracing technique
Huber's group studied the binding of α-synuclein with vesicles, using their Electron Paramagnetic Resonance (EPR) technique. They placed several labels on the molecule, and by manipulating their electron spins they could keep track of the labels’ positions during the process. In this way, they monitored the behavior of the protein. They measured the mobility of the labels to determine which parts of the protein have maximum binding, and therefore move the least.

Surprise
‘Much to my amazement it turns out that α-synuclein binds surprisingly well,’ says Huber. ‘Normally speaking, this kind of vesicles binds poorly because it is not very negatively charged. Still, we see this result.’ It provides a piece of the puzzle to figure out the cause of Parkinson’s disease. Huber: ‘The occurrence of a disease has many factors, including the truly malicious processes, but also correction mechanisms of the body that work correctly or fail. We need to map out all those pieces of the puzzle to see where exactly things take a turn for the worse. Now we see that α-synuclein plays an important role in Parkinson’s. You have a much better chance of finding a treatment once you understand how a disease works, so it is important that we came a step closer towards getting the full picture.’

 

The protein α-synuclein (green) is plastered with labels on several sites. By manipulating the labels’ electron spins (red), it becomes clear with which site and how strongly the protein binds with the membrane. 

 

Neurotransmitters (purple balls) are trapped inside vesicles (brown circles). During the transfer of neurotransmitters, the vesicle attaches to the brain membrane (brown edge around grey area), so that an opening emerges towards the synapsis (white area between nerve cell below and nerve cell on top). In the brain of patients with Parkinson’s disease something goes wrong in this process, and α-synuclein turns out to play a major role in this. The protein proves to bind strongly with the concerning vesicles, which boosts the suspicion that they have something to do with the disease. Photo Credit: Gayla S. Keesee

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