New discovery as to what causes Parkinson’s disease

A major discovery has been made that will create a new way to treat this neurodegenerative disease which has seen the highest increase in cases globally.

One of the world’s leading Parkinson’s disease scientists has warned of a potential pandemic of the neurological condition if research doesn’t “step up” to address the looming crisis.

Professor David Komander, head of WEHI’s Ubiquitin Signalling Division, said Parkinson’s was growing at a faster rate than the more common Alzheimer’s disease.

“We do need to do something about it because it is clear Parkinson’s is a neurodegenerative disease with the highest increase in cases globally,” he said.

It comes as the WEHI team he leads saw in action for the first time a human mitochondrial protein called PINK1 that is linked to Parkinson’s disease.

Professor Komander said the major breakthrough, published in the journal Science on Friday, was giving a molecular picture of the process that has gone wrong in people living with Parkinson’s.

The potential, he said, was to accelerate new drugs to stop the disease.

The role of PINK1 is to “tag” damaged mitochondria for disposal, but when it mutates it can’t function properly and this can cause Parkinson’s.

A hallmark of the disease is the death of brain cells and a malfunctioning PINK1 the likely culprit.

PINK1 research team L–R: Professor David Komander, Dr Nicholas Kirk, Dr Sylvie Callegari and Dr Alisa Glukhova. Image: WEHI

Professor Komander said the discovery was a huge leap forward in the fight against Parkinson’s.

He said it allows researchers to see what human PINK1 looks like, how it attaches to the surface of damaged mitochondria and switches on.

Parkinson’s is an insidious progressive movement disorder of the nervous system.

It affects around 200,000 Australians with 50 new diagnoses a day. Existing medications can help control symptoms, but there is no cure.

Professor Komander said for 25 years scientists have known PINK1 was linked to Parkinson’s.

“What has eluded us was to really see human PINK1 with our own eyes, structurally,” he said.

The next step is that we are able to see how drugs may bind to PINK1 to stabilise it in this environment.”

Professor Komander said this was an important part in the drug discovery process. “To be able to see how your drug binds, or where you can improve your molecule in order to make it even better,” he said.

“And I think that is eventually the hope that we can give Parkinson’s patients, because there’s no treatment right now.

“What we really need is something that stops or slows the progression of Parkinson’s and that really is the next frontier in this research space.”

First author and mitochondria biologist Dr Sylvie Callegari said the breakthrough was developing a method of purifying PINK1.

“I realised that in order to solve this, we had to scale up and use a brute force approach to get this protein complex out of cells and to visualise it,” Dr Callegari said.

“It was certainly worthwhile because we solved not one big problem in the field, but actually several.”

The team show PINK1 proteins attached to the membrane of a mitochondrion for the first time. Image: WEHI

Dr Callegari says PINK1 works in four distinct steps, including sensing mitochondrial damage.

“This is the first time we’ve seen human PINK1 docked to the surface of damaged mitochondria and it has uncovered a remarkable array of proteins that act as the docking site,” she said.

“We also saw how mutations present in people with Parkinson’s disease affect human PINK1.”

The research team hopes to use the knowledge to find a drug to slow or stop Parkinson’s.

Originally published as New discovery as to what causes Parkinson’s disease