Horseshoe protein linked to Parkinson's

Martina Huber, a biophysicist at Leiden University, was the first person to discover that a protein that is partly responsible for Parkinson’s disease can have a horseshoe configuration. This is an exceptional discovery because the protein is practically invisible. Martina Huber, a biophysicist at Leiden University, was the first person to discover that a protein that is partly responsible for Parkinson’s disease can have a horseshoe configuration. This is an exceptional discovery because the protein is practically invisible.

Accumulatiaon of proteins in the brain

With Parkinson’s and Alzheimer’s disease an accumulation of proteins is found in the brain. Fragments of a protein with the complicated name of alpha-synuclein are found in these plaques. It is unknown what the role of these proteins is in this accumulation, but it has recently been discovered that the protein that often accumulates looks like an entwined horseshoe. This gives us some indication of how the proteins accumulate: horseshoe-shaped proteins can easily become tangled together.

Shape determines effectiveness

Martina Huber discovered the aggregate of this horseshoe protein. ‘In order to understand the cause of Parkinson’s and Alzheimer’s, for example, it is important to know which shapes the protein can assume, because the shape helps determine the effectiveness of the protein,’ says Huber. ‘But when and where you find the molecule and in what shape is also important.’ And that was a big problem with the protein that Huber studies, because for a long time it was an invisible and almost untraceable molecule. It proved difficult to determine its structure, at least with the available technology such as electron microscopy.

Detour

Huber therefore had to take a detour. ‘Once the protein had been produced and labelled in Vinod Subramaniam’s research group (Universiteit Twente),with which we collaborated in this project, we labelled the protein and then measured the distance between the labels. That was so successful that we now have an idea of the natural shape of the molecule. In the case of the protein that accumulates in patients with Parkinson’s and Alzheimer’s, this proved to be a structure that is similar to a horseshoe.’

Lead

That the protein assumes the horseshoe shape and can thus stick together may be a lead in the search for a remedy, the Leiden biophysicist suggests. ‘But I’d rather not make any predictions about how the discovery might help with the development of drugs for Parkinson’s or Alzheimer’s.’