Boosting waste disposal to prevent Parkinson’s
New Parkinson’s UK research aims to harness the brain’s self-cleaning system to wash away toxic proteins and stop the condition in its tracks.
While we’re awake our brain cells are busy, hard at work coordinating the messages that govern everything we do. This constant activity creates waste, which if it’s allowed to build up, can cause problems. Fortunately, when we sleep it gives the brain some much needed time off and a chance for the clear, colourless fluid that surrounds it — called the cerebrospinal fluid — to filter through, rinsing away the debris generated during the day.
This recently discovered self-cleaning process is called the glymphatic system and this nightly deep-clean may be the reason why sleep is so crucial to brain health.
Now, research jointly funded by Parkinson’s UK and Alzheimer’s Research UK and led by Dr Ian Harrison at University College London will investigate whether boosting the brain’s self-cleaning system could be the key to new treatments.
One of the key features in both conditions is the gradual build-up of toxic proteins — in Parkinson’s the main offender is alpha-synuclein — which are believed to play a major role in damaging brain cells.
Recent research in mice has suggested that it may be possible to stimulate the glymphatic system with exercise and small amounts of alcohol to help clear toxic proteins linked to Alzheimer’s.
This new project will build upon these promising findings and investigate whether boosting the glymphatic system with drug-like molecules can help the brain rid itself of toxic proteins, and whether this could protect it from damage.
We caught up with Ian to find out more about the 3 year project and what he hopes to achieve.
Where did the idea for this project come from?
“In Parkinson’s, a protein called alpha-synuclein builds up inside the cells which control movement in the brain. This is extremely toxic for brain cells and ultimately leads to their death.
“Recent research suggests that alpha-synuclein is ejected from affected cells and absorbed by their neighbours and may be to blame for the spread of problems through the brain. Stopping this domino-like progression could be the key to stopping the relentless march of the condition.
“We know that the the glymphatic system can help clear away some of the proteins that build up in other conditions — such as beta-amyloid in Alzheimer’s. But we don’t yet know whether alpha-synuclein can be cleared by this same system.
“Some initial experiments we’ve done suggest that it can. So, in this project, we will investigate whether or not we can harness the glymphatic system to reduce the build up of alpha-synuclein in the brain in Parkinson’s.”
Can you tell us a bit more about the project?
“To do this we will study a specific mouse model of Parkinson’s, in which the speed and severity of alpha-synuclein spread throughout the brain can be measured.
“These mice are genetically engineered so that their brain cells make a large amount of alpha-synuclein protein. Then by injecting a small amount of a special toxic form of the protein we can trigger the spread throughout the brain which is similar to what happens in people with Parkinson’s.
“By blocking the function of the glymphatic system with drugs in these mice, we’ll be able to firstly tell if this system influences how alpha-synuclein spreads through the brain.
“Following on from this, we’ll test a range of drug-like molecules which have been shown by other scientists to speed up glymphatic function in the brain. We will measure how they affect the spread of alpha-synuclein in the brain and we will look to see whether the mice show changes in movement-based symptoms.
“By the end of the project we’ll therefore know whether or not targeting the glymphatic system, holds hope as a possible cure for Parkinson’s.”
If the project is successful how could it lead to better treatments?
“If we’re successful, and one or more of the treatment strategies tested in the final part of the project successfully block spread of alpha-synuclein in the mouse brain, it would be a major breakthrough.
“Because our experiments will be done in mice, the next step would be more in-depth laboratory studies to understand how safe and effective this kind of treatment might be for people with Parkinson’s. Further work would also be required to further refine and optimise the therapies before they could go forward to be tested in people in clinical trials.”