Written and posted by : Bhawana Jain
Published on: January 24, 2017
Article Source: University of Nottingham
Abstract: A fault with the body’s natural waste disposal system which helps to keep our brain cell ‘batteries’ healthy may contribute to neurodegenerative disease, says new research.
A fault with the body’s natural garbage disposal system which helps to keep our brain cell ‘batteries’ healthy may contribute to neurodegenerative disease, says new research.
The research was carried out by the researchers of the University of Nottingham and has been published in the journal Cell Death and Disease, centres on problems with mitochondria — the powerhouses which produce energy within a cell.
The current research supports previous evidence in which patients with Parkinson’s Disease were found to have faults with brain mitochondria which led to dysfunction and death within their neurons.
“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,” says Dr. Lynn Bedford, in the University’s School of Life Sciences.
“If waste is not removed it will build up over time and become toxic, causing cells to go wrong and eventually die,” he adds.
These faults in the cell disposal system may play a crucial role in neurodegenerative diseases like Parkinson’s and Alzheimer’s as they are caused by the death of neurons — the network through which information is transferred in our brain.
The researchers used gene targeting in mice and discovered that a faulty UPS in neurons leads to damaged mitochondria that produce less energy. These damaged mitochondria are also found 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 research also showed 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 study was carried out 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.
Aslihan Ugun-Klusek, Michael H Tatham, Jamal Elkharaz, Dumitru Constantin-Teodosiu, Karen Lawler, Hala Mohamed, Simon M L Paine, Glen Anderson, R John Mayer, James Lowe, E Ellen Billett, Lynn Bedford. Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway. Cell Death and Disease, 2017; 8 (1): e2531 DOI: 10.1038/cddis.2016.443