A discovery about a critical protein linked to Parkinson’s disease could underpin new treatments for the incurable disease.

WEHI researchers have visualised the entire process that leads to the activation of PINK1 – a protein directly linked to the early onset of Parkinson’s disease. The discovery solves a decade-long mystery and provides the first detailed blueprint for identifying potential treatments that could slow or even stop the progression of Parkinson’s disease.

Unprecedented view

Parkinson’s disease is a progressive neurodegenerative disease that currently impacts more than 10 million people worldwide. A cure for the condition is yet to be found, with available therapies only able to treat and alleviate symptoms. PhD student Zhong Yan Gan said the research provided an unprecedented view of a protein called PINK1 with incredible molecular detail, leading to a better understanding of how defects in this protein could trigger Parkinson’s disease.

“Our research has essentially produced a ‘live action’ movie that reveals the entire activation process of PINK1. There are tens of thousands of scientific papers on this protein family, but to visualise how PINK1 comes together and changes in the activation process is a worldfirst,” Mr Gan said.

Custom-built facility

Study co-lead Dr Alisa Glukhova said the discovery was made possible thanks to a new custom-built cryo-EM facility jointly funded by WEHI and Bio21 Institute, and WEHI’s recruitment of structural biologists with expertise in using cryo-EM technology.

“The revolutionary technique has only been available in the past five years. It is a great example of how innovative technologies can really drive forward research and lead to transformative discoveries,” she said.

Therapeutic potential

Professor David Komander said his lab’s discovery paved the way for developing therapeutic agents that ‘switch on’ PINK1 to treat Parkinson’s disease.

“Biotech and pharmaceutical companies are already looking at PINK1 and this pathway as a therapeutic target for Parkinson’s disease, but they’ve been flying a bit blind.

“I think the new structures that our team has been able to produce using cryo-EM will provide that muchneeded clarity. I’m really proud of this work and where it may lead,” he said.