Parkinson’s disease is the fastest growing neurodegenerative condition in the world, affecting over 10 million people globally. It is the second most common neurodegenerative disease after Alzheimer’s, and currently, there is no cure. But thanks to a recent breakthrough, scientists hope that new treatments may soon be on the horizon.
The disease is linked to a protein called PINK1 because people with Parkinson's have a mutation in a gene called PARK6, which encodes this protein.
Faults in the way PINK1 functions have been directly linked to Parkinson's disease, especially in people when it is early-onset, which makes up about 1.2 per cent of individuals with Parkinson's in the UK.
Scientists have recently made strides in understanding how PINK1 interacts with mitochondria. Anyone familiar with biology textbook lingo will know mitochondria as "the powerhouse of the cell" as they produce energy inside the cells of all living things.
The link between PINK1 and Parkinson’s disease has been known for a long time but scientists have never known enough about it to help with a Parkinson's cure, until now.
When mitochondria become damaged, PINK1 notices this and signals to the body that they should be removed – but in people with Parkinson’s disease, the faulty mitochondria go undetected and accumulate, where they begin releasing toxins and eventually kill the cell.
Now, researchers at the Walter and Eliza Hall (WEHI)’s Parkinson’s Disease Research Centre in Australia have worked out what PINK1 looks like, how it is activated and how it interacts with faulty mitochondria, publishing their findings in Science today.
“This is a significant milestone for research into Parkinson’s,” said corresponding author Professor David Komander, head of WEHI’s Ubiquitin Signalling Division, in a statement. “It is incredible to finally see PINK1 and understand how it binds to mitochondria.
“Our structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson’s.”
Lead author and WEHI senior researcher Dr Sylvie Callegari explained that PINK1 works in four distinct steps – the first two of which had not been seen by scientists until this study.
First, PINK1 senses mitochondrial damage. Then, it attaches itself to faulty mitochondria. After that, it signals with a small protein called ubiquitin that the mitochondria need to be removed. Finally, ubiquitin links to a protein called Parkin so that the damaged mitochondria can be recycled in a process called mitophagy.
“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,” said Callegari. “We also saw, for the first time, how mutations present in people with Parkinson’s disease affect human PINK1.”
Parkinson’s is a neurological condition. One of its hallmarks is the death of brain cells, because this PINK1-mitochondria relationship is particularly important in the brain.
Brain cells need a lot of energy, so they tend to contain more mitochondria than most cells elsewhere in the body. That means that brain cells are especially sensitive to damage from toxins released by faulty mitochondria. When brain cells die, they are also replaced at much lower rates than cells elsewhere, leading to neurological decline.
Parkinson’s disease has doubled in prevalence in the past 25 years, according to the World Health Organization, and rates are expected to continue rising dramatically. The authors of this study are hoping that their research will help speed up the development of drugs to stop Parkinson’s in its tracks.
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