A Parkinson’s Protein's Live Views Could Lead to New Treatments

The team uncovered the mysterious relationship between the disease and the protein.
Can Emir
3d rendered image of neuron cells system disease.koto_feja/iStock

Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) at the  Department of Medical Biology of The University of Melbourne, have solved a mystery about Parkinson’s disease, which can help create novel treatments for the disease.

Led by Ph.D. student Zhong Yan Gan and Professor David Komander from WEHI, used state-of-the-art cryo-electron microscopy (cryo-EM) to visualize the protein called PINK1.

PINK1 protein normally protects cells by demolishing and recycling damaged mitochondria. When there are defects in PINK1 or other components of this process, it prevents the replacement of the mitochondria thus starving the cell of energy.

PINK1 malfunctions are estimated to be important for young people who develop Parkinson’s due to hereditary mutations of the protein.

“The team then used the images to create a “live-action” view of the activation of the protein, thus providing information about how Parkinson’s disease kills or impairs the nerves that produce dopamine. The research has also been published in the journal Nature.

“Many papers from laboratories around the world – including ours – have captured snapshots of the PINK1 protein," first author Zhong Yan Gan told WEHI news. "However, the differences in these snapshots have in some ways fueled confusion about the protein and its structure. What we have been able to do is to take a series of snapshots of the protein ourselves and stitch them together to make a ‘live-action’ movie that reveals the entire activation process of PINK1. We were then able to reconcile why all these previous structural images were different – they were snapshots taken at different moments in time as this protein was activated to perform its function in the cell." he added.

“Biotech and pharmaceutical companies are already looking at this protein and this pathway as a therapeutic target for Parkinson’s disease, but they have been flying a bit blind. I think they’ll be really excited to see this incredible new structural information that our team has been able to produce using cryo-EM. I’m really proud of this work and where it may lead” Professor Komander said.

There are many ongoing studies regarding the currently untreatable Parkinson’s disease. A recent study conducted in UC San Francisco Weill Institute for Neurosciences analyzed 11 years' worth of data and scientists discovered a link between disrupted circadian rhythm and Parkinson's. While researchers at the University of California reported a one-time gene therapy permanently reversed Parkinson’s symptoms in a mouse model of the disease.

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