A discovery led by OHSU was made possible by years of study conducted by University of Portland undergraduates.
Scientists have discovered a natural compound that can halt a key process involved in the progression of certain cancers and demyelinating diseases—conditions that damage the protective myelin sheath surrounding neurons, such as multiple sclerosis (MS).
A study published in the Journal of Biological Chemistry identified a plant-derived flavonoid called sulfuretin as an inhibitor of an enzyme linked to both MS and cancer. The research, conducted in cell models at Oregon Health & Science University, demonstrated that sulfuretin effectively blocked the enzyme's activity. The next phase of research will involve testing the compound in animal models to evaluate its therapeutic potential, effectiveness, and possible side effects in treating cancer and neurodegenerative diseases like MS.
A Potentially Wide-Reaching Treatment
"We think this is a drug that could have impact in a lot of different areas," said Larry Sherman, Ph.D., professor in the Division of Neuroscience at OHSU's Oregon National Primate Research Center.
The researchers found that sulfuretin, along with a pair of synthetic compounds that were also tested in live cells, inhibited the activity of a particular type of enzyme known as a hyaluronidase, which naturally degrades hyaluronic acid. That's important because when hyaluronic acid is broken down into fragments, it is known to cause problems in at least two ways:
- Forestalls myelin repair: It prevents the maturation of oligodendrocytes, which are cells that produce myelin. Myelin is the protective sheath covering each nerve cell's axon — the threadlike portion of a cell that transmits electrical signals between cells. Damage to myelin is associated with MS, stroke, brain injuries, and certain forms of dementia. In addition, delay in myelination can affect infants born prematurely, leading to brain damage or cerebral palsy.
- Allows cancer cells to proliferate: In cancerous tumors, hyaluronidase activity can allow cancer cells to proliferate unchecked by normal cellular death. "Now we have an inhibitor that could actually stop that," said Sherman, who is also a professor of cell, developmental, and cancer biology in the OHSU School of Medicine.
The new research focuses on inhibiting a specific type of hyaluronidase known as cell migration-inducing and hyaluronan-binding protein, or CEMIP.
In addition to MS and cancer, CEMIP is implicated in a range of disorders, including osteoarthritis, skin infections, brain injury caused by heavy alcohol use, and possibly other neurodevelopment disorders, including Alzheimer's disease. The study indicates its activity appears to be inhibited by sulfuretin.
Molecules in flowers
The discovery came after years of undergraduates painstakingly screening plant compounds in the lab of co-author Angela Hoffman, Ph.D., a longtime and now-retired professor of chemistry at the University of Portland.
"Over the years, her students have been grinding up these flowers, extracting molecules, and testing to see if any of them blocked hyaluronidase activity," Sherman said. "Finally, a couple of years ago, they found a compound that was promising."
Alec Peters, a graduate student in Sherman's lab at OHSU, found that this compound blocked CEMIP activity in a tumor cell line and in oligodendrocyte progenitor cells. Oligodendrocytes generate myelin.
Hoffman, a nun and chemistry professor who earlier this year retired from the University of Portland after 35 years to lead her convent, began collaborating with Sherman a decade ago. Over that time, she said, hundreds of undergraduate students worked on breaking down dozens of plants to their molecular essence and then testing to see whether any of the compounds worked to neutralize CEMIP.
The new publication validates the students' diligent work over many years, she said.
"Directing the students to be able to do this kind of research helps them in their careers," Hoffman said. "This discovery could be useful for Alzheimer's or other neurodegenerative conditions. As long as the underlying problem relates to hyaluronic acid being broken apart, this could be helpful for people."
Reference: "Distinct chemical structures inhibit the CEMIP hyaluronidase and promote oligodendrocyte progenitor cell maturation" by Alec Peters, Fatima Banine, Kanon Yasuhara, Angela Hoffman, Prashant K. Basappa, Lily Metri, Ava Gunning, Jake Huffman, Clinton C. VanCampen, Stephen A. Shock and Larry S. Back, 24 October 2024, Journal of Biological Chemistry.
DOI: 10.1016/j.jbc.2024.107916
The research was supported by the National Institutes of Health, grant award P51 OD011902 for the operation of the Oregon National Primate Research Center at OHSU; Congressionally Directed Medical Research Programs grant award MS160144; the National Multiple Sclerosis Society, grant award RG 4843A5/1; the National Institute of Neurological Disorders and Stroke of the NIH, grant award NS054044; and the National Institute of Alcohol Abuse and Alcoholism of the NIH, grant award P60AA010760.
News
New book from NanoappsMedical Inc – Molecular Manufacturing: The Future of Nanomedicine
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
A Virus Designed in the Lab Could Help Defeat Antibiotic Resistance
Scientists can now design bacteria-killing viruses from DNA, opening a faster path to fighting superbugs. Bacteriophages have been used as treatments for bacterial infections for more than a century. Interest in these viruses is rising [...]
Sleep Deprivation Triggers a Strange Brain Cleanup
When you don’t sleep enough, your brain may clean itself at the exact moment you need it to think. Most people recognize the sensation. After a night of inadequate sleep, staying focused becomes harder [...]
Lab-grown corticospinal neurons offer new models for ALS and spinal injuries
Researchers have developed a way to grow a highly specialized subset of brain nerve cells that are involved in motor neuron disease and damaged in spinal injuries. Their study, published today in eLife as the final [...]
Urgent warning over deadly ‘brain swelling’ virus amid fears it could spread globally
Airports across Asia have been put on high alert after India confirmed two cases of the deadly Nipah virus in the state of West Bengal over the past month. Thailand, Nepal and Vietnam are among the [...]
This Vaccine Stops Bird Flu Before It Reaches the Lungs
A new nasal spray vaccine could stop bird flu at the door — blocking infection, reducing spread, and helping head off the next pandemic. Since first appearing in the United States in 2014, H5N1 [...]
These two viruses may become the next public health threats, scientists say
Two emerging pathogens with animal origins—influenza D virus and canine coronavirus—have so far been quietly flying under the radar, but researchers warn conditions are ripe for the viruses to spread more widely among humans. [...]
COVID-19 viral fragments shown to target and kill specific immune cells
COVID-19 viral fragments shown to target and kill specific immune cells in UCLA-led study Clues about extreme cases and omicron’s effects come from a cross-disciplinary international research team New research shows that after the [...]
Smaller Than a Grain of Salt: Engineers Create the World’s Tiniest Wireless Brain Implant
A salt-grain-sized neural implant can record and transmit brain activity wirelessly for extended periods. Researchers at Cornell University, working with collaborators, have created an extremely small neural implant that can sit on a grain of [...]
Scientists Develop a New Way To See Inside the Human Body Using 3D Color Imaging
A newly developed imaging method blends ultrasound and photoacoustics to capture both tissue structure and blood-vessel function in 3D. By blending two powerful imaging methods, researchers from Caltech and USC have developed a new way to [...]
Brain waves could help paralyzed patients move again
People with spinal cord injuries often lose the ability to move their arms or legs. In many cases, the nerves in the limbs remain healthy, and the brain continues to function normally. The loss of [...]
Scientists Discover a New “Cleanup Hub” Inside the Human Brain
A newly identified lymphatic drainage pathway along the middle meningeal artery reveals how the human brain clears waste. How does the brain clear away waste? This task is handled by the brain’s lymphatic drainage [...]
New Drug Slashes Dangerous Blood Fats by Nearly 40% in First Human Trial
Scientists have found a way to fine-tune a central fat-control pathway in the liver, reducing harmful blood triglycerides while preserving beneficial cholesterol functions. When we eat, the body turns surplus calories into molecules called [...]
A Simple Brain Scan May Help Restore Movement After Paralysis
A brain cap and smart algorithms may one day help paralyzed patients turn thought into movement—no surgery required. People with spinal cord injuries often experience partial or complete loss of movement in their arms [...]
Plant Discovery Could Transform How Medicines Are Made
Scientists have uncovered an unexpected way plants make powerful chemicals, revealing hidden biological connections that could transform how medicines are discovered and produced. Plants produce protective chemicals called alkaloids as part of their natural [...]
Scientists Develop IV Therapy That Repairs the Brain After Stroke
New nanomaterial passes the blood-brain barrier to reduce damaging inflammation after the most common form of stroke. When someone experiences a stroke, doctors must quickly restore blood flow to the brain to prevent death. [...]
