A new study by University of Chicago researchers shows how two proteins interact with each other to help protect the survival of neurons involved in sensing touch. The findings represent a step toward better understanding the mechanisms of neuroprotection, a process that plays an important role in neurodegenerative diseases like Alzheimer’s.
In a study using roundworms as a model organism, researchers discovered a new protein, called LRON-11, and showed how it binds with another well-known protein, teneurin. When scientists blocked this interaction, the worms’ mechanosensory (or touch-sensing) neurons lost their ability to protect themselves from degeneration.
Similar proteins and interactions occur on the surfaces of human neurons, raising potential implications for human health, noted senior author Demet Araç, PhD, Professor of Biochemistry and Molecular Biology at UChicago.
“Protecting neuronal health is extremely important for preventing many diseases,” she said. “Our study is a first step to revealing which cell surface proteins might be important.”
A new role for teneurins
Neurons do not regenerate, so protecting neuronal health and survival is extremely important, noted co-corresponding author Engin Özkan, PhD, Associate Professor of Biochemistry and Molecular Biology. The breakdown of neuroprotection is linked with Alzheimer’s and other neurodegenerative diseases.
Teneurins belong to a class of proteins that reside on the surfaces of neurons and help cells connect to one another. They are known to be involved in synapse formation and wiring in the human brain. This study is the first time teneurins have been shown to also play a role in protecting neuron health and survival.
For the new study, researchers screened proteins found in roundworms to look for unexpected interactions. They noticed that a teneurin called TEN-1 interacted with LRON-11, a previously unstudied protein.
When they studied this interaction in cells, they found that teneurin and LRON-11 interacted with each other to form a complex structure. The first author in the study, Jingxian Li, PhD, research scientist in the Araç and Özkan labs, said, “We solved the three-dimensional high-resolution structure of the binary complex using cryogenic electron microscopy and also showed that this complex could be broken with point mutations.”
To understand the biological function of this interaction, the team collaborated with the laboratory of Andrea Calixto, PhD, in Chile, who was studying neurodegeneration and mechanosensation in C. elegans, or roundworms. Previous research had found a link between neuroprotection and the microbiome; when worms were fed a diet that supported their microbiota, it helped prevent the degeneration of neurons involved in sensing touch.
For the new study, researchers examined how teneurin and LRON-11 affected this process. They modified the genes of worms to eliminate teneurin, or LRON-11, or block the two proteins from binding to each other. They found that without the interaction of teneurin and LRON-11, the worms’ microbiomes lost their neuroprotective effect.
Implications for human health
Although neuroprotection is studied in humans, much is still unknown about the mechanism of how it works at the molecular level, Özkan said.
“We found two proteins that reside on neuronal surfaces that bind to each other, and the complex they make is necessary for the development and survival of these mechanosensitive neurons,” he said. “We now have two genes whose presence is necessary for neuroprotection.”
Araç noted that another team of researchers is working on a similar study documenting the same interaction in fruit flies, where it seems to play an important role in the flies’ ability to smell.
“This interaction does not only exist in C. elegans, and it’s important for different biological functions,” she said.
The researchers are working on follow-up studies to understand this mechanism in greater detail, including where the proteins are located within the brain and on neuronal surfaces, what they respond to, and how the microbiome affects their function.
The paper, “The teneurin TEN-1 and its ligand LRON-11 support microbiota-induced neuroprotection and mechanosensory function in C. elegans,” was published Sept. 21, 2026, in Current Biology.
