Scottish scientists make Parkinsons fight discovery

Researchers at the University of Dundee have found links between the genetic causes of Parkinson’s at a molecular level.

The University of Dundee's MRC Protein Phosphorylation and Ubiquitylation Unit has conducted extensive research into Parkinson's disease. Photo: MRC-PPU.

Vital molecular “switches” which regulate cell growth and survival have been found to be the missing link in explaining why some people are afflicted with Parkinson’s disease later in life.

The switches, known as “Rabs”, are controlled by the PINK1 gene which has a direct link to the likelihood of contracting the disease. This discovery suggests that it may be possible to treat Parkinson’s through the creation of drugs that manipulate Rabs.

The presence of mutations in the PINK1 gene, which otherwise helps create a natual barrier against Parkinson’s disease, can result in the deterioration of brain cells which control basic motor function. The breakthrough discovery of these molecules was made by the university’s Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU).

Until this research was completed, it was not known which targets PINK1 could turn on and off. Dundee’s team, led by Dr Miratul Muqit and Dr Matthias Trost, analysed tens of thousands of signals using state-of-the-art technology.

They found that the PINK1 enzyme simultaneously targets a switchboard of Rabs to change their activity and protect patients from the effects of the debilitating condition.

Dr Muqit said “Parkinson’s disease is at present incurable and it is vital we understand the molecular mechanisms in order to design the next generation of therapeutics against the disease.

“In previous work we had outlined a single pathway for PINK1 but the discovery of an entire family of Rabs as PINK1 targets indicates a more complex network of pathways that, if disrupted, renders brain cells vulnerable to stress and ultimately to the development of Parkinson’s.

“Using state-of-the-art technology, we were able to pinpoint how a single gene affects a few proteins among tens of thousands of possible targets. It was like finding the proverbial needle in the haystack.”

Dr Trost added, “In the future it will be critical to study this molecular ‘switchboard’ in more detail in Parkinson’s patients. That said, our new research strongly suggests that developing drugs to modulate Rabs represents an exciting new approach to treating Parkinson’s.”

Various organisations dedicated to research into a cure for the disease have welcomed the report, including the Wellcome Trust, Parkinson’s UK and the Michael J. Fox Foundation. The latter organisation was founded in 2000 after the Back to the Future movie star was diagnosed with the condition in the 1990s.

Dr Arthur Roach, Director of Research at Parkinson’s UK, which helped fund the study, said, “People with Parkinson’s recognise that the greatest need is for treatments that stop or reverse the condition at an early stage.

“This study points to some proteins that may be changed early in Parkinson’s, and suggests ways to design drugs that could stop it in its tracks.”

The University of Dundee-led paper has been published in The EMBO Journal and was co-authored with Professor Aymelt Itzen of the Technical University of Munich and Drs Olga Corti and Jean Christophe Corvol of the Brain and Spine Institute of Paris.