Abstract
TRPA1, a versatile ion channel of the Transient Receptor Potential (TRP) channel family, detects a large variety of chemicals and can contribute to signal processing of other stimuli, e.g., due to its sensitivity to cytosolic calcium elevation or phosphoinositolphosphate modulation. At first, TRPA1 was found on sensory neurons, where it can act as a sensor for potential or actual tissue damage that ultimately may elicit pain or itch as warning symptoms. This review provides an update regarding the analgesic and antipruritic potential of TRPA1 modulation and the respective clinical trials. Furthermore, TRPA1 has been found in an increasing amount of other cell types. Therefore, the main focus of the review is to discuss the non-analgesic and particularly the disease-modifying potential of TRPA1. This includes diseases of the respiratory system, cancer, ischemia, allergy, diabetes, and the gastrointestinal system. The involvement of TRPA1 in the respective pathophysiological cascades is so far mainly based on pre-clinical data.
Highlights
TRPA1, a versatile ion channel of the Transient Receptor Potential (TRP) channel family, detects a large variety of chemicals and can contribute to signal processing of other stimuli, e.g., due to its sensitivity to cytosolic calcium elevation or phosphoinositolphosphate modulation
The present review considers targeting TRPA1 in clinical studies for a specific disease and lists evidence for TRPA1 as a potential therapeutic target in diseases not yet addressed in clinical studies, considering non-analgesic potential
Amgen published trichloro(sulfanyl)ethyl benzamides as potent TRPA1 antagonists, which were more than 10 times more potent in human compared to rat TRPA1 [11]
Summary
Since its cloning [1], description of its role in the sensory system [2], phenotyping of the knockout animals [3], and determination of the majority of the structure [4], Transient receptor potential cation channel subfamily A member 1 (TRPA1) has been the topic of several reviews. These were more general [5] or more topical, e.g., with a molecular perspective [6]. The review discusses potential side effects of TRPA1 modulation, which could prevent, or at least largely limit, its therapeutic use
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