Diverting cells’ energy pathway could pave way for new Parkinson’s treatments

  • Researchers from the University of Sheffield have found a fundamental switch in metabolism as neurons mature is altered by gene changes which cause Parkinson's Disease
  • Diverting a cells energy pathway and boosting mitochondria function could help to prevent or delay effects of the neurodegenerative disease
  • 145,000 people in the UK are living with Parkinson’s disease and it is estimated one in 37 of us will develop it in our lifetime

Parkinson's Disease

Scientists from the University of Sheffield have found that switching or boosting the energy source of matured cells in Parkinson's disease patients, could pave the way for new treatments.

As human cells mature, they seek energy from mitochondria - the cells’ batteries - which are known to be defective in people with Parkinson’s disease. The new research, funded by Parkinson's UK, has found that directing cells to get energy from other sources, or boosting mitochondria function, could help to prevent or delay effects of the neurodegenerative disease.

The findings, published today (Wednesday 23 September 2020) in Scientific Reports, have given scientists a better understanding of mitochondrial function and further research will now look to identify ways to divert the cell's energy pathway to mitigate the effect of the parkin mutation which is present in people with Parkinson’s.

Parkinson’s disease is the second most common neurodegenerative disease, with approximately 10 million people affected worldwide. Currently, only symptomatic treatment options are available to patients.

Dr Heather Mortiboys, Senior Lecturer at the University of Sheffield’s Institute of Translational Neuroscience (SITraN) and Senior Research Fellow for Parkinson's UK, explains: “Mitochondria are the cell batteries and are known to be defective in Parkinson's. Our study has found, for the first time, that mitochondrial defects are only revealed when neurons mature and are reliant on their mitochondria to power them.

“Parkin is involved in recycling dysfunctional mitochondria in the cell, so if parkin doesn't work properly, dysfunctional mitochondria are not efficiently cleared. This study has shown this is only the case if the cells rely on the mitochondria for their energy supply, in cells which can use other energy generating pathways, dysfunctional mitochondria are recycled via alternative pathways.

“This has implications for how easily different pathways can generate the energy the cell needs, and importantly the recycling of defective mitochondria.”

In this study scientists used cells taken from Parkinson’s patients with a mutation in the parkin gene to generate the type of brain cells affected in the disease - the dopaminergic neuron. The research found that a switch as the neurons mature shifts the energy status of the cell towards mitochondria which means that parkin mutant cells then struggle to maintain energy levels.

Mitochondria are the cell batteries and are known to be defective in Parkinson's. Our study has found, for the first time, that mitochondrial defects are only revealed when neurons mature and are reliant on their mitochondria to power them

Dr Heather mortiboys, sheffield institute of translational neuroscience 

This research could pave the way for new Parkinson’s treatments in the future as it has shown several alterations to mitochondrial function in patient derived neurons are possible.

The study provides evidence that small molecules already in clinical trials for other conditions may be beneficial in Parkinson's research. Researchers have shown that compounds targeted at mitochondrial diseases are effective at restoring the oxidative balance of the neurons without restoring full mitochondrial function.

Future research will test compounds affecting several steps of the mitochondrial pathways identified here in these and other patient derived cells.

Claire Bale, Head of Research at Parkinson’s UK, said: “We’re delighted to be supporting this promising, groundbreaking research.

“This study adds a new layer to our understanding of what goes wrong inside brain cells in Parkinson’s and could lay the foundations for developing new treatments.

"We’re working with Dr Mortiboys through our pioneering Virtual Biotech programme to create new treatments targeting mitochondria which could slow or stop Parkinson’s - something no currently known treatment can do.”

The research forms part of the work of the University of Sheffield’s Neuroscience Institute, which aims to bring academics and scientists together from across varied specialties to translate scientific discoveries from the lab into pioneering treatments that will benefit patients living with neurodegenerative disorders.

Additional information 

The University of Sheffield

With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world’s leading universities.

A member of the UK’s prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines.

Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in.

Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2018 and for the last eight years has been ranked in the top five UK universities for Student Satisfaction by Times Higher Education.

​​Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.

Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

 Contact

For further information please contact:

Emma Griffiths
Media and PR Assistant
The University of Sheffield
0114 222 1034
e.l.griffiths@sheffield.ac.uk