(ORDO NEWS) — The PIEZO1 mechanoreceptor, one of the proteins for which the 2021 Nobel Prize was awarded, has been found to be the main culprit in itch that occurs in response to skin irritation.
Last year’s Nobel Prize in Physiology or Medicine team continues to study receptor proteins. In the new work, Ardem Patapoutian and colleagues have shown that some sensory neurons are able to perceive mechanical irritation of the skin, creating an itch sensation. The reaction is triggered by the PIEZO1 protein, a mechanoreceptor that perceives weak pressure.
Itching can be caused by both chemical and mechanical irritants – poison ivy juice that has got on the skin, insects crawling on it, or “prickly” fibers of woolen clothing.
This feeling allows you to get rid of insects and other skin-damaging influences. However, some allergy sufferers suffer from excessive itching, and if it comes to eczema, then an unbearable desire can make you comb the sore to the blood.
It is believed that different protein molecules that work in different cells of the body are responsible for the occurrence of this sensation. Some of them, responding to chemical irritation with histamine, were identified some time ago.
And now, the team of Ardem Pataputyan from the Scripps Institute has shown that the PIEZO1 mechanoreceptor responds to mechanical stimulation .
For his study of PIEZO1, the closely related PIEZO2, and other receptors, Pataputian received the 2021 Nobel Prize in Physiology or Medicine. However, the role of this protein in the occurrence of itching was rather unexpected.
These proteins are expressed in many different cells of the body and are located on their membranes. They “feel” the deformation of the membrane and trigger cascades of signaling reactions, thanks to which we perceive weak touches on the skin, feel the position of the joints or the fullness of the bladder.
At the same time, PIEZO1 is not produced in nerve receptor cells, with the exception of some not very numerous groups.
In the new work, Pataputian and colleagues have shown that the protein is made and works in neurons associated with itching. Laboratory mice, in which PIEZO1 activity was increased, became very sensitive to skin irritation. Conversely, animals with suppressed PIEZO1 protein reacted to stimulation much weaker.
Curiously, the change in PIEZO1 activity slightly changed the irritability in response to irritants. This may be due to the fact that the protein is involved in both the “mechanical” and “chemical” pathways of itch. This is yet to be confirmed.
In addition, the scientists are going to find out how small differences in PIEZO1 activity in different populations of people affect their sensitivity to itching.
In particular, in Africans resistant to infection with malarial plasmodium, the level of PIEZO1 is slightly elevated. Perhaps these manifestations are somehow connected.
But the main thing, perhaps, is that the new work may lead to the creation of drugs that relieve severe itching in some patients.
Scientists have already demonstrated the ability of certain substances to reduce the function of PIEZO1, but in the future, more specific agents may appear that block the protein and the irritation it causes.
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