Scientists at the Medical Research Council (MRC) Protein Phosphorylation Unit at the University of Dundee have discovered a new molecular switch that acts to protect the brain from developing Parkinson’s disease.
The findings have helped scientists understand how genetic mutations in a gene called PINK1 lead to Parkinson’s in patients as young as 8 years old - which could eventually lead to new ways to diagnose and treat the condition.
The job of some proteins inside cells is to switch other important proteins on or off. Understanding how these proteins work and which proteins they target could be the key to why nerve cells die in Parkinson’s – and how we can save them.
But despite intensive research, the target of the PINK1 enzyme (which is made by the PINK1 gene) has eluded scientists for almost a decade.
Now the Dundee team has found that PINK1 switches on a protein called Parkin, whose main job is to keep cells healthy by removing damaged proteins. Mutations in the gene that makes Parkin can also cause inherited forms of Parkinson’s in younger patients .
The team was led jointly by Dr Miratul Muqit and Professor Dario Alessi at the University of Dundee.
“Parkinson’s is a devastating degenerative brain disorder and currently we have no drugs in the clinic that can cure or slow the disease down,” said Dr Muqit, a Wellcome Trust Clinician Scientist in the MRC Protein Phosphorylation Unit.
“Over the last decade, many genes have been linked to Parkinson’s but a major roadblock has been determining the function of these genes in the brain and how the mutations lead to brain degeneration.”
Dr Muqit said, “Our work suggests this pathway can’t be switched on in Parkinson’s patients with genetic mutations in PINK1 or Parkin. More research will be needed to see whether this also happens in Parkinson’s patients who do not carry these mutations.”
Professor Alessi, Director of the MRC Protein Phosphorylation Unit, added, “Now that we have identified this pathway, the key next step will be to identify the nature of these damaged proteins that are normally removed by Parkin. Although further studies are required, our findings also suggest that designer drugs that switch this pathway on could be used to treat Parkinson’s.”
The research was funded by the Medical Research Council, Wellcome Trust, Parkinson’s UK, the J. Macdonald Menzies Charitable Trust and the Michael J. Fox Foundation.
The research is published in the latest edition of the journal Open Biology. The paper was co-authored with Dr Helen Walden from Cancer Research UK’s London Research Institute.
NOTES TO EDITORS
LIFE SCIENCES AT DUNDEE
With more than 1000 scientists, research students and support staff from 58 countries and external funding in excess of £30 million per year, the College of Life Sciences at the University of Dundee is one of the largest and most productive Life Sciences research institutes in Europe. Consistently voted one of 'the best places for a life scientist to work' by The Scientist magazine, the College has an international reputation for its basic and translational research and was recognised in the 2011 Biotechnology and Biological Sciences Research Council Excellence with Impact Awards for 'Greatest Delivery of Impact'. The University of Dundee is the central hub for a multi-million pound biotechnology sector in the east of Scotland, which now accounts for 16% of the local economy.
About Parkinson’s UK
127,000 people in the UK have Parkinson’s. It is a progressive neurological condition for which there is currently no cure. As the leading Parkinson’s research and support charity we are currently funding around90 groundbreaking research projects worth £15 million across England, Scotland, Wales and Northern Ireland.
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.