A fault with the natural waste disposal system that helps to keep our brain cell ‘batteries’ healthy may contribute to neurodegenerative disease, a new study has found.
The research, led by academics at The University of Nottingham and published in the journal Cell Death and Disease, centres on problems with mitochondria – the powerhouses which produce energy within a cell.
The results support previous evidence that patients with Parkinson’s Disease have faults with brain mitochondria which contributes to dysfunction and death within their neurons.
Dr Lynn Bedford, in the University’s School of Life Sciences, said: “The study highlights the importance of the ubiquitin proteasome system (UPS) for healthy mitochondria. The UPS is like a waste disposal system that removes small unwanted proteins from inside cells.
“If waste is not removed it will build up over time and become toxic, causing cells to go wrong and eventually die.”
Faults in this system may play an important role in neurodegenerative diseases such as Parkinson’s and Alzheimer’s because they are caused by the death of neurons – the network through which we transfer information in our brain.
Using gene targeting in mice, the researchers have discovered that a faulty UPS in neurons leads to damaged mitochondria that produce less energy. Damages mitochondria are also known to produce harmful molecules that injure the cell – oxidative stress – so it is vital that the brain is able to keep mending, removing and replacing them.
The study also found that when the UPS was faulty, the damaged mitochondria were not removed from neurons in the normal way by the process of autophagy, the disposal system that breaks down larger parts in the cell like mitochondria.
The research was conducted in collaboration with experts at Nottingham Trent University, the University of Dundee, Nottingham University Hospitals NHS Trust and Great Ormond Street Hospital for Children NHS Trust in the UK and the University of Tripoli in Libya.
A copy of the research paper, Continued 26S proteasome dysfunction in mouse braincortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway, is available online.
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Notes to editors: The University of Nottingham has 43,000 students and is ‘the nearest Britain has to a truly global university, with a “distinct” approach to internationalisation, which rests on those full-scale campuses in China and Malaysia, as well as a large presence in its home city.’ (Times Good University Guide 2016). It is also one of the most popular universities in the UK among graduate employers and was named University of the Year for Graduate Employment in the 2017 The Times and The Sunday Times Good University Guide. It is ranked in the world’s top 75 by the QS World University Rankings 2015/16, and 8th in the UK for research power according to the Research Excellence Framework 2014. It has been voted the world’s greenest campus for four years running, according to Greenmetrics Ranking of World Universities.
More information is available from Dr Lynn Bedford in the School of Life Sciences, University of Nottingham on +44 (0)115 0115 823 0099, [email protected]ac.uk
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