TRPA1 Linked to Asthma

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Asthma involves an immune response to inhaled allergens and chemical irritants, but the limited efficacy of existing treatments aimed at modifying this response suggest that additional physiological mechanisms may be at work in the disease process. In a report published in the May 19th online Early Edition of PNAS, US researchers have now found that the ion channel, TRPA1, plays a key role in allergic asthma. cigarette smokeTRPA1 is a ‘chemosensor’ that is activated by mustard oil as well as by a number of endogenous and exogenous stimuli known to be triggers of asthmatic inflammation. The team found that, compared with wild type mice, animals that did not express TRPA1 showed fewer asthma symptoms, with reduced inflammation, airway mucus and bronchoconstriction. Although the exact role of TRPA1 in asthmatic inflammation is not yet understood, the ion channel is known to be activated by allergens such as cigarette smoke that can trigger asthma attacks. TRPA1 is found in airway nerves and the researchers believe that blocking TRPA1 may prevent infiltration of the lung by the inflammatory cells responsible for asthma symptoms such as wheezing and overproduction of mucus. HC-030031 structureIn further studies, the team went on to show that treatment with the TRPA1 antagonist, HC-030031, reduced the symptoms of allergic asthma in mice. TRPA1 antagonists have previously been shown to reduce chronic inflammatory and neuropathic pain. The discovery of a role for TRPA1 as a neuronal mediator of allergic airway inflammation could lead to new treatments for allergic asthma and Hydra Biosciences, whose scientists contributed to the study, hope to start human clinical trials with a novel TRPA1 inhibitor within 12 months.


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