UNIVERSITY of Dundee scientists have made strides that they say could lead to drugs that benefit patients with Parkinson’s.
The team of scientists have uncovered the inner relay of a molecular switch which provides protection from the development of Parkinson’s disease to the brain.
Parkinson’s is the quickest growing brain disorder globally but at this time there is no treatments which can slow it down or halt it.
The university’s previous research discovered that a gene called PINK1 is vital for protecting brain cells against stress and that mutations of this gene removes this protection, leading to Parkinson’s symptoms.
PINK1 is categorised as a class of enzyme called a kinase, it functions as a sensor for any damage to the power generators of cells known as mitochondria.
It then switches on a protective pathway through targeting two key proteins called ubiquitin and Parkin which clears the damage, though how PINK1 was switched was not known before.
In research now published in the journal Science Advances, Dundee scientists working with researchers in the UK, Netherlands and Germany, uncovered a model of the inner workings of how PINK1 is switched on.
This was uncovered with biological and artificial intelligence methods and revealed how the PINK1 switch is activated through binding to key parts of a complex machine on the mitochondria’s surface.
This complex machine is known as the Translocase of outer membrane (TOM) complex, these findings show that PINK1 uses unique elements not seen in other enzymes.
These make up a relay switch which activate PINK1, enabling it to target ubiquitin and Parkin which exerts its protective function against Parkinson’s.
Professor Miratul Muqit, Consultant Neurologist at the School of Life Sciences at Dundee stated: “As a clinician who treats Parkinson’s patients, the goal of our research is to discover fundamental mechanisms that may point to new ways to better treat the disease in the future.
“Our new findings add to a number of emerging treatment strategies targeting the PINK1 pathway, some that are now entering clinical trials for Parkinson’s patients this year.
“This work provides a framework to undertake future studies directed at finding new drug-like molecules that can target PINK1 at the TOM complex.”
Professor Dario Alessi, Director of the MRC-PPU, said: “This is bold and painstaking molecular research which allows us to better understand the biology that underlies Parkinson’s disease, and provides new ideas on how PINK1-controlled Parkinson’s disease could be better diagnosed and treated, opening the door for further important research.”
This research received funding from the Wellcome Trust, Aligning Science Across Parkinson’s (ASAP), The Michael J. Fox Foundation for Parkinson’s Research (MJFF), and the Medical Research Council.
