Written by Munia Awni, this article was selected as a winner of our 2023 High School Science Communication Challenge. Awni is a student at Dubai College in Dubai, United Arab Emirates.
The Brain at Night
Despite the thoughts that cloud your mind, you still wake up with a fresh brain thanks to a built-in brain mechanism called the glymphatic system that clears out the waste produced by neurons. As we participate in daily activities, our brain cells take in large amounts of energy and release unwanted debris in the brain that can build up, become toxic, and cause damage to neurons that prevents them from carrying out their functions. Luckily, the brain has a filtration system to get rid of the waste produced — essentially, this is our brain’s version of taking out the trash.
Above: Schematic depicting how the glymphatic system eliminates waste from the brain. Image courtesy of Harvard University.
This filtration becomes an issue for people with Parkinson’s disease because it corrodes their neurons’ ability to produce dopamine. Dopamine is vital in allowing nerve cells to communicate with each other by acting as a chemical messenger. Therefore, the decreased production of dopamine in Parkinson’s patients leads to their escalating loss of motor skills, causing tremors and a lack of balance. Currently, the main treatment for Parkinson’s is the drug Levodopa, which is used to stimulate neurons into making dopamine, consequently increasing the dopamine supply in the brain. This treatment usually improves the motility problems Parkinson’s patients face.
Although it is unclear what causes the neurons to become impaired or die, there are studies that suggest that the toxic accumulation of a protein called alpha-synuclein can induce damage to the membrane of the neurons that then kills them. This turning point in the study of Parkinson’s has led to a bloom in research and experiments toward treatments that involve boosting the brain’s cleaning system. Research done by Parkinson’s UK and Alzheimer’s Research UK serves as an example. These organizations discovered, by testing on mice, that exercise and small portions of alcohol aid in clearing the brain of toxic proteins.
Mutation Determination
A recent discovery by researchers at the University of Queensland has identified that mutations occurring on a specific gene — Endophilin A1, which correlates with an increased risk of Parkinson’s disease — contribute to the decline of the brain’s cleaning system. Fundamentally, genes are small sections of DNA that contain a set of instructions that allow your cells to make different protein molecules your body needs. Dr. Adekunle Bademosi, the project’s lead researcher, states that the mutation in the Endophilin A1 gene “blocks the process by which the body and brain recycle cell waste” by making the protein that begins the cleaning of the built-up debris insensitive to triggers.
The Queensland University researchers discovered this anomaly by showing that mutations in the Endophilin A1 gene lead to Drosophila with an inhibited brain-cleaning process. Without the brain’s self-cleaning process, the debris continues to build up, allowing the toxic proteins to debilitate and kill neurons — a known cause of the development of Parkinson’s. This discovery could revolutionize future treatments for Parkinson’s, as it explains exactly how the glymphatic system is affected by a gene mutation that is associated with the disease.
The Future
Dr. Bademosi suggests that “it may be time to shift the treatment focus to autophagy as the mechanism underlying these disease hallmarks”, highlighting a new direction for Parkinson’s treatments that target the glymphatic system’s decline and the reasons underlying this decline. Dr. Bademosi further proposes exploring “compounds that induce or inhibit autophagy” to produce more effective drugs. Two hundred years since Parkinson’s was first classified, treatment for the disease is now taking a new and more effective course thanks to this remarkable discovery by these University of Queensland researchers.