WEHI researchers have made a huge leap forward in the fight against Parkinson\u2019s disease, solving a decades-long mystery that paves the way for development of new drugs to treat the condition.<\/p>\n
First discovered over 20 years ago, PINK1 is a\u00a0protein\u00a0directly\u00a0linked to\u00a0Parkinson\u2019s disease \u2013 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.\u00a0<\/p>\n
In\u00a0a major breakthrough, researchers at the WEHI Parkinson\u2019s Disease Research Centre have determined the first ever structure of human PINK1 bound to mitochondria, in findings published in\u00a0Science. The work could help find new treatments for the condition that currently has no cure or drug to stop its progression.<\/p>\n
In a world-first, WEHI researchers have discovered what human PINK1 looks like and how it is activated.PINK1 is a protein linked to Parkinson\u2019s disease, the second most common neurodegenerative disease after Alzheimer\u2019s.There is no cure for Parkinson\u2019s.This discovery, published inScience, is a huge leap forward in the fight against Parkinson\u2019s with the hope that it will accelerate the search for a drug to stop the condition.<\/p>\n
Parkinson\u2019s disease is insidious, often taking years, sometimes decades to diagnose. Often associated with tremors, there are close to 40 symptoms including cognitive impairment, speech issues, body temperature regulation and vision problems.<\/p>\n
In Australia, over 200,000 people live with Parkinson\u2019s and between 10% and 20% have Young Onset Parkinson\u2019s Disease \u2013 meaning they are diagnosed under the age of fifty. The impact of Parkinson\u2019s on the Australian economy and healthcare systems is estimated to be over $10 billion each year.<\/p>\n
Breakthrough after decades of research<\/p>\n
Mitochondria produce energy at a cellular level in all living things, and cells that require a lot of energy can contain hundreds or thousands of mitochondria. The PARK6 gene encodes the PINK1 protein, which supports cell survival by detecting damaged mitochondria and tagging them for removal.<\/p>\n
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.<\/p>\n
Although PINK1 has been linked to Parkinson\u2019s, and in particular Young Onset Parkinson\u2019s Disease, researchers had been unable to visualise it and did not understand how it attaches to mitochondria and is switched on.<\/p>\n
Corresponding author on the study and head of WEHI\u2019s Ubiquitin Signalling Division, Professor David Komander, said years of work by his team have unlocked the mystery of what human PINK1 looks like, and how it assembles on mitochondria to be switched on.<\/p>\n
\u201cThis is a significant milestone for research into Parkinson’s. It is incredible to finally see PINK1 and understand how it binds to mitochondria,\u201d\u00a0said Prof Komander, who is a laboratory head in the WEHI Parkinson\u2019s Disease Research Centre.<\/p>\n
\u201cOur structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson\u2019s.\u201d<\/p>\n
Hope for future treatments<\/p>\n
Lead author on the study, WEHI senior researcher Dr Sylvie Callegari, said PINK1 works in four distinct steps, with the first two steps not been seen before.<\/p>\n
First, PINK1 senses mitochondrial damage. Then it attaches to damaged mitochondria. Once attached it tags ubiquitin, which then links to a protein called Parkin so that the damaged mitochondria can be recycled.<\/p>\n