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Protein in sensory nerves acts as sensor for mechanical itch

The protein PIEZO1 in sensory nerves appears to be a key detector of mechanical itch—as opposed to chemically-induced itch caused by histamine, for example—according to a paper published in Nature.

This is the first identification of a cause for mechanical itch, which refers to the sensations of crawling insects or other irritating objects that touch the skin. The scientists at Scripps Research in La Jolla, Calif., suggest that this discovery could potentially lead to the development of PIEZO1 inhibitors for the treatment of conditions such as psoriasis and atopic dermatitis.

“These findings help us untangle the complexity of itch sensation, and suggest that PIEZO1 inhibitors could be very useful clinically,” study senior author Ardem Patapoutian, PhD, said in a press release. He is a professor in the Department of Neuroscience at Scripps Research and a Howard Hughes Medical Institute investigator.

In experiments, mice with an overactive form of PIEZO1 were significantly more sensitive to itch sensations, while mice lacking PIEZO1 in their sensory neurons scratched themselves far less when their skin was stimulated using filaments.

The researchers also showed that a PIEZO1-blocking compound could alleviate scratching behaviours in mice with the equivalent of eczema.

“We did see a dramatic effect on itch with this compound, and though it wasn’t specific enough against PIEZO1 to develop into a drug, we hope eventually to develop a much more PIEZO1-specific compound for treating itch conditions,” reported first author Rose Hill, PhD in the press release.

Dr. Patapoutian won a share of the 2021 Nobel Prize for Medicine or Physiology for research on PIEZO1 and its sister-protein PIEZO2 conducted in his laboratory at Scripps. They are now investigating whether variants of the PIEZO1 gene in humans are related to itch sensitivity.


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