August 8, 2022

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Discovery of mechanical itch protein could lead to new treatments for eczema

Discovery of mechanical itch protein could lead to new treatments for eczema



 

Discovery of mechanical itch protein could lead to new treatments for eczema.

Scientists studying the cellular basis of itch have made an important discovery that could lead to new treatments for chronic conditions such as eczema.

At the heart of this breakthrough is mechanical itch, and the research team behind it has shown how to block a protein to reduce itching in a mouse model of the condition.

 

Discovery of mechanical itch protein could lead to new treatments for eczema.

 

 

Much of the itch we experience as humans is driven by activation of the histamine system.

This system releases histamine as part of the body’s response to things like mosquito bites, pollen or certain medications, and also produces the type of itching and redness we often see as triggers for these.

While this form of “chemical itch” has been studied for a long time, recently scientists have begun to turn their attention to a separate phenomenon known as “mechanical itch”.

 

Mechanical pruritus is produced by the application of light stimulation. In conditions like eczema, mechanical stimulation through scratching increases inflammation, which in turn increases itching, creating a vicious cycle of irritation.

Scientists have already begun working on possible interventions in this area, as a 2019 study identified neuronal pathways responsible for regulating mechanical itch.

 

This latest study, conducted by scientists at Scripps Research, has now identified a protein in the sensory nerve that acts as a “sensor” of mechanical itch.

This is the first discovery of a mechanical itch protein that stems from earlier work on the ion channel protein PIEZO1 in the outer cell membrane, which opens in response to mechanical deformation.

 

Research has begun to show that PIEZO1 is expressed at low levels in certain subpopulations of sensory neurons, and the Scripps team has an important new elaboration on this idea.

Through experiments in mice, the team showed that PIEZO1 acts as a pressure-sensitive ion channel protein in two types of sensory neurons that have been identified as having a role in chemical itch.

 

The researchers found that mice with an overactive form of PIEZO1 felt more sensitive to mechanical itch, while mice lacking the protein responded much less to their own scratching.

The scientists were then able to show that using a compound to block PIEZO1 reduced scratching in a mouse model of eczema.

 

“We did see a dramatic effect on itch with this compound, and while it’s not specific enough for PIEZO1 to be developed as a drug, we hope to eventually develop a more PIEZO1-specific compounds for the treatment of pruritus.”

 

In the case of PIEZO1, there does appear to be some overlap between chemical and mechanical itch. When raising and lowering the activity of PIEZO1, the scientists reported, they also saw a decrease and increase in scratching due to chemical itch triggers, albeit on a smaller scale.

It does, however, suggest that mechanical and chemical itch signaling share some of the same neuronal pathways.

 

While more work is needed for researchers to translate these findings into clinical treatments for conditions such as eczema, the findings do advance their understanding of itch.

As part of next steps, the scientists are now investigating the potential relationship between variants in the PIEZO1 gene and itch sensitivity in humans.

 

“These findings help us unravel the complexities of itching perception, and additionally suggest that PIEZO1 inhibitors could be very useful in the clinic,” said Ardem Patapoutian, another author of the research paper.

 

 

 

Discovery of mechanical itch protein could lead to new treatments for eczema.

(source:internet, reference only)


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