University of Utah researchers have identified a molecule that can treat Parkinson’s disease
Daniel Scholes, assistant professor of neurology, and Stefan Bolst, chair of the department of neurology, discuss a newly identified molecule that could help treat Parkinson’s disease and slow its progression. (University of Utah Health)
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SALT LAKE CITY – Scientists at the University of Utah Health have made a discovery that could lead to a new way to treat Parkinson’s disease and potentially halt its progression.
Daniel Scholes, associate professor of neuroscience at the university, and his team of researchers recently published a report on the discovery in the Journal of Biological Chemistry, detailing how the molecule slows cells’ production of a protein called alpha-synuclein.
In a healthy brain, alpha-synuclein is thought to help neurons communicate. However, in unhealthy brains, this protein clumps – or clumps together – within neurons to form small, slender fibers called fibroblasts, which are thought to lead to the death of dopamine-producing neurons and can lead to neurodegenerative disorders such as Parkinson’s disease and Lewy body dementia. or multiple system atrophy.
Dopamine is a neurotransmitter, which means it acts as a messenger between nerve cells and is involved in moving the body, learning, memory, sleeping and waking, and even mood regulation. When the neurons that produce dopamine die, people can develop Parkinson’s disease A disorder of the central nervous system that affects movement and balance, sometimes causing tremors. infects more than 10 million people around the world It is degenerative, so symptoms get worse as the disease progresses and more nerve cells die.
Current treatments for Parkinson’s disease are drugs that work similarly to dopamine and can help send these messages between nerve cells to control symptoms, but there is no current treatment for the disease or any way to stop its progression.
Although the death of neurons in Parkinson’s disease remains somewhat of a mystery, researchers have been looking at alpha-synuclein as the culprit, so the ability to slow the production of the toxic protein may help slow the death of those neurons and thus slow down how quickly it occurs. Neurodegeneration.
“Most cases of Parkinson’s disease are characterized by an overabundance of alpha-synuclein,” Scholes said. “The prevailing thinking is that if you lower its overall abundance, this will be a cure.”
Duong Huynh, an assistant professor in the University of Utah’s Department of Neuroscience, used gene-editing tools to insert a firefly gene that encodes a light-producing protein into human genes. When the protein is turned on, it makes human cells glow whenever the alpha-synuclein gene is active and dim when it is less active.
Scholes and Huynh worked with Stefan Paulst, chair of the university’s department of neurology, and researchers at the National Center for Advanced Translational Sciences to use these light-producing cells to perform millions of evaluations to see how a variety of small molecules might. It affects the alpha-synuclein gene.
The team used an automated setup to evaluate 155,885 different compounds at the center’s facility.
They determined that a molecule called A-443654 could likely suppress protein production. Huynh died in 2018, and a postdoctoral researcher named Mandi Gandelman ran further tests and discovered that the molecule slows down the alpha-synuclein gene in human cells and also reduces the gene’s production of the alpha-synuclein protein.
The molecule can also relieve the stress that alpha-synuclein puts on cells that could cause them to die. Gandelman explained that this drop in stress on the cell may allow the cells to break up the clumps that have already formed.
“We can shut down production, but we also need to reduce the total that is already there,” Gandelman says. “The more this builds up, the more toxic it becomes.”
The team plans to conduct further research to see if the molecule could be developed into a potential treatment for Parkinson’s disease and other neurodegenerative disorders that involve clumps of the alpha-synuclein protein. They will also check for other molecules they found during their tests that might block alpha-synuclein production.
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