Lead Investigator: Professor Jeremy Henley
Institution: University of Bristol
Grant type: PhD studentship
Grant amount: £79,452
Start date: October 2013
Completion date: December 2016
Scientific Title: Can protein SUMOylation be neuroprotective in Alzheimer’s disease?
What was the project, and what did the researchers do?
Alzheimer’s disease is characterised by cognitive impairment and memory loss. This occurs when the brain cells, called neurons, either start to die or have a problem in their ability to communicate with each other. It has been reported previously that a particular process known to control some of the proteins in the neurons, called SUMOylation, plays an important role in some of the negative effects in the brain of people with Alzheimer’s disease.
SUMOylation is the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. It regulates how proteins interact with each other and depending on the circumstances can either promote or hinder this interaction.
The researchers in this project used brain tissue samples to compare the levels of SUMO and associated proteins in the brain of people with Alzheimer’s disease, and healthy controls, to better understand the changes that occur in Alzheimer’s disease.
Using the information from these samples the team then used neuronal cells in the lab to look further at the differences seen in the brains of people with Alzheimer’s disease, to understand the role of proteins in the progression of Alzheimer’s.
What were the key results, and how will this help in the fight against dementia?
This study looked at two areas of the brain, the prefrontal cortex which is known to be significantly affected in Alzheimer’s disease, and the cerebellum which is thought to be less affected. There was no change in the levels of the SUMO proteins between healthy controls and brains of people with Alzheimer’s disease. This doesn’t necessarily mean that SUMOylation doesn’t play a role in the progression of Alzheimer’s disease, but it means that further investigation is required.
The team did find a decrease of the levels of a particular protein called Dynamin related protein 1 (Drp1) in the prefrontal cortex but not in the cerebellum. Drp1 is a target of the SUMO proteins. Drp1 is important in the growth of new mitochondria, the parts of all cells that provide energy, an essential process for the busy neurons.
The researchers looked at the role of Drp1 in the neurons of Alzheimer’s disease. They treated the cells with the toxic fragment of amyloid, which is known to form the plaques in the brains of people with Alzheimer’s disease. This reduced the amount of Drp1, similar to that seen in the brain tissue samples. Lastly they found that artificially reducing the amount of Drp1 reduced the ability of the neurons to communicate with each other, which is fundamentally important for memory.
Better understanding of the differences between healthy brains and those of people with Alzheimer’s disease, will not only help understanding of the progression of the disease, but will also help to develop new and better treatments.
What happened next? Future work and additional grants
The researchers believe this is a promising avenue of investigation and will continue to look in to the potential role of Drp1 SUMOylation on neurons in the brains of people affected by Alzheimer’s disease.
How were people told about the results? Conferences and Publications
• 5th Conference on Advances in Molecular Mechanisms Underlying Neurological Disorders, 2014
• Alzheimer’s Society Annual Research Conference, 2014
• Alzheimer’s Society Legacy Event, 2014
• Alzheimer’s Society Annual Research Conference 2015
• GW4 away day in Bristol, 2015
• 5th European Synapse meeting, 2015
• 10th FENS forum of Neuroscience, 2016