Researchers at Johns Hopkins Medicine have discovered a previously unknown role of proteasomes, traditionally known as the cell's waste processors, in nerve cells. Their findings, published in Cell Reports, reveal that proteasomes in dorsal root ganglion neurons may act as signal messengers, aiding in the differentiation between pain and itch sensations.

Proteasomes are typically viewed as cellular garbage disposals, responsible for breaking down proteins into smaller bits and recycling them. However, the study conducted by the Johns Hopkins researchers suggests that proteasomes in neuronal membranes serve a much more important function.

By blocking proteasomes with specific inhibitors in mice, the researchers observed significant changes in sensory response, indicating the proteasomes' crucial role in environmental sensing and neuronal communication. Mice that were injected with the proteasome-blocking drug were between 25% to 50% slower in responding to sensory tests on one side of their body.

The researchers used single-cell sequencing technology to identify the presence of membrane proteasomes in a subpopulation of neurons involved in itch sensation and known to be sensitive to histamine, an immune system compound that triggers response to allergens. When these membrane proteasomes were blocked, the activity of all cells changed, suggesting that proteasomes facilitate communication between these cells.

This discovery challenges the traditional view of proteasomes as simple garbage disposals and expands our understanding of their essential role in sensory neurons. The researchers believe that manipulating membrane proteasomes in neurons could potentially alter pain and itch sensations, presenting a promising target for therapeutic interventions.

It is worth noting that proteasome blockers, including a drug called Velcade, are already being utilized for treating certain types of cancer. This suggests a potential pathway for repurposing these drugs for sensory disorders.

Moving forward, the researchers plan to explore how neuronal membrane proteasomes function in sensory neurons and their role in distinguishing between pain and itch sensations. They aim to investigate whether manipulating membrane proteasomes can lead to different outcomes in sensory perception.

The research was funded by the National Institutes of Health (NIH) and a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center. Further contributions came from scientists at Johns Hopkins including Samuel Kho, Taylor Church, Anna Brennan, Fulya Türker, Michael Delannoy, and Michael Caterina.

This ground-breaking study not only expands our understanding of proteasome functions but also opens new avenues for the development of targeted treatments for sensory disorders. With further research and exploration, scientists may be able to harness the potential of proteasomes to improve the lives of individuals experiencing sensory problems.