Parkinson’s disease breakthrough

Parkinson’s disease is a movement disorder that generally affects people over the age of 60. Its prevalence increases with age, and it is estimated to affect one in 40 people aged 85-90.  

More than 150,000 Australians live with the disease, which is the fastest growing neurodegenerative condition in the world. 

Between 10% and 20% have young onset Parkinson’s, meaning they are diagnosed under the age of 50. The impact of Parkinson’s on the Australian economy and healthcare systems is estimated at more than $10 billion a year. 

There is no cure for Parkinson’s, and research progress into it has been glacial, with mystery surrounding a key protein directly linked to the disease.  

Until now, no one had seen what the protein, human PINK1, looks like, how it attaches to the surface of damaged mitochondria, or how it is switched on. 

In a breakthrough, researchers at the Walter and Eliza Hall Institute of Medical Research Centre (WEHI) in Melbourne, have determined the first ever structure of human PINK1 bound to mitochondria. 

Published in the Science journal, the work could help find new treatments for the condition that currently has no cure or drug to stop its progression. 

Researchers expect their discovery to accelerate the search for a drug to stop the condition. 

Parkinson’s is an insidious disease, taking years, sometimes decades to diagnose. It is often associated with tremors, but there are close to 40 symptoms, including cognitive impairment, speech issues, body temperature regulation, and vision problems. 

The breakthrough concerns mitochondria, which produce energy at a cellular level in all living things. Cells that require a lot of energy can contain hundreds or thousands of mitochondria.  

In a healthy person, when mitochondria are damaged, PINK1 gathers on mitochondrial membranes and signals through a small protein called ubiquitin, that the broken mitochondria need to be removed. 

The PINK1 ubiquitin signal is unique to damaged mitochondria, and when PINK1 is mutated in patients, broken mitochondria accumulate in cells. 

Study author, Professor David Komander, said years of work by his team had unlocked some of PINK 1’s key mysteries. 

“It is incredible to finally see PINK1 and understand how it binds to mitochondria,” he said. “Our structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson’s.” 

This is the first time researchers have seen human PINK1 docked to the surface of damaged mitochondria and uncovered proteins that act as the docking site. 

They also saw, for the first time, how mutations present in people with Parkinson’s disease affect human PINK1. 

One of the hallmarks of Parkinson’s is the death of brain cells. Around 50 million cells die and are replaced in the human body every minute. But unlike other cells in the body, when brain cells die, the rate at which they are replaced is extremely low. 

When mitochondria are damaged, they stop making energy and release toxins into the cell. In a healthy person, the damaged cells are disposed of in a process called mitophagy. 

In a person with Parkinson’s and a PINK1 mutation, the mitophagy process no longer functions correctly and toxins accumulate in the cell, eventually killing it. Brain cells need a lot of energy and are especially sensitive to this damage.