The development solves a a decades-long mystery and paves the way for development of new drugs to treat the condition.
The development solves a a decades-long mystery and paves the way for development of new drugs to treat the condition.
In an important breakthrough for people living with Parkinson’s, a Australian study has finally determined the structure of a protein linked to an early-onset form of the disease.
Solving a decades-long mystery that paves the way for development of new drugs to treat the condition, the study, published in the journal Science, shows how a protein – PINK1 – attaches to the surface of damaged mitochondria.
First discovered over 20 years ago, PINK1 is a protein directly linked to Parkinson’s disease – the fastest growing neurodegenerative condition in the world.
Until now, no one had seen what human PINK1 looks like, how PINK1 attaches to the surface of damaged mitochondria, or how it is switched on.
The new insight could help researchers find a drug to slow or stop Parkinson’s in people with a PINK1 mutation.
“This is a significant milestone for research into Parkinson’s,” the study’s co-author Professor David Komander of the WEHI Parkinson’s Disease Research Centre, Australia said.
“It is incredible to finally see PINK1 and understand how it binds to mitochondria,” Komander added.
“Our structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson’s.”
Parkinson’s disease is the second most common neurodegenerative disease in the world behind Alzheimer’s.
By 2050, it is projected that 25.2 million people will be living with the disease, posing a significant public health challenge.
It is associated with more than 40 symptoms, including tremors, cognitive impairment, speech issues, body temperature regulation and vision problems.
While Parkinson’s typically effects people over the age of 60, a subset of patients are diagnosed before the age of 50 with young-onset Parkinson’s (YOP).
PINK1 gathers on the surface of mitochondria, the energy-producing organelles inside cells.
parkinson's
Two PINK1 proteins shown attached to the membrane of a mitochondrion for the first time.
When mitochondria are damaged, they stop making energy and release toxins into the cell. In a healthy person, PINK1 tags these damaged mitochondria with a protein (ubiquitin) which signals to the cell that they need to be removed.
But this doesn’t happen in a person with YOP whose PINK1 is mutated.
Instead, damaged mitochondria and toxins accumulate, eventually killing the cells. And brain cells, which need a lot of energy, are especially sensitive to this damage.
Until now, researchers had been unable to visualise PINK1 and did not understand how it attaches to mitochondria and is switched on, limiting their ability to develop drugs to restore its function.
“This is the first time we’ve seen human PINK1 docked to the surface of damaged mitochondria,” says lead author of the study and WEHI senior researcher, Dr Sylvie Callegari.
“It has uncovered a remarkable array of proteins that act as the docking site,” Callegari said.
“We also saw, for the first time, how mutations present in people with Parkinson’s disease affect human PINK1.”
This article was originally published by Cosmos Magazine . Read the original here.