A natural compound found in everyday fruits and vegetables may hold the key to protecting nerve cells — and it’s showing promise as a potential treatment for ALS (amyotrophic lateral sclerosis) and dementia, according to new research from the University of Missouri.

“It’s exciting to discover a naturally occurring compound that may help people suffering from ALS or dementia,” said Smita Saxena, a professor of physical medicine and rehabilitation at the School of Medicine and lead author of the study. “We found this compound strongly impacted maintaining motor and muscle function and reducing muscle atrophy.”

The study discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries, and endives, may support nerve cell health and holds promise as a potential treatment for ALS.

In lab-grown nerve cells from ALS patients, the compound helped the cells produce more energy and ease stress in the protein-processing center of the cell called the endoplasmic reticulum. Additionally, the compound improved overall cell function and slowed nerve cell damage.

Researchers found that kaempferol worked by targeting a crucial pathway that helps control energy production and protein management—two functions disrupted in individuals with ALS.

“I believe this is one of the first compounds capable of simultaneously targeting both the endoplasmic reticulum and mitochondria,” Saxena said. “By interacting with both of these components within nerve cells, it has the potential to elicit a powerful neuroprotective effect."

The challenge

The catch? The body doesn’t absorb kaempferol easily, and it could take a lot to see real human benefits. For instance, an individual with ALS would need to consume at least 10-11 pounds of kale in a day to obtain a beneficial dose.

“Our bodies don’t absorb kaempferol very well from the vegetables we eat,” Saxena said. “Because of this, only a small amount reaches our tissues, limiting its effectiveness. We need to find ways to increase the dose of kaempferol or modify it so it’s absorbed into the bloodstream more easily.”

Another hurdle is getting the compound into the brain. The blood-brain barrier — a tightly locked layer of cells that blocks harmful substances — also makes it harder for larger molecules like kaempferol to pass through.

What’s next?

Despite its challenges, kaempferol remains a promising candidate for treating ALS, primarily because it works even after symptoms start. It also shows potential for other neurodegenerative diseases, including Alzheimer’s and Parkinson’s.

To make the compound easier for the body to absorb, Saxena’s team at the Roy Blunt NextGen Precision Health building is exploring ways to boost its uptake by neurons. One promising approach involves packaging lipid-based nanoparticles — tiny spherical particles made of fats that are commonly used in drug delivery.

“The idea is to encapsulate kaempferol within lipid-based nanoparticles that are easily absorbed by the neurons,” Saxena said.  “This would target kaempferol to neurons to greatly increase its beneficial effect.”

The team is currently generating the nanoparticles with hopes of testing them by the end of the year.

The study, “Kaempferol enhances ER-mitochondria coupling and protects motor neurons from mitochondrial dysfunction and ER stress in C9ORF72-ALS,” was published in Acta Neuropathologica Communications. Other authors from Mizzou are Paulien Hermine Smeele and Julieth Andrea Sierra-Delgado, both with the Department of Physical Medicine and Rehabilitation.

Article by Sara Diedrich - University of Missouri

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