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DIVERSE ACTIVATORS AND OUTCOMES. "TRPA1 was found to be activated by a variety of chemical compounds, including mustard oil and cannabinoids. Subsequent studies identified additional ligands and revealed roles in pain, inflammation, itch, mechanical sensation, oxygen regulation, and more." https://lnkd.in/e-WBvC9 View in LinkedIn

MOLECULAR MAPPING. "The molecular determinants of temperature sensing in TRPV1 have been located in the N terminal domain in the pore turret, in the outer pore region, and in the C terminal. TRPV1 and TRPV2... are heat receptors with different temperature thresholds and share an amino acid identity of about 70%." https://lnkd.in/eZQCjnY View in LinkedIn

TOXINEERING. "The researchers identified a tarantula spider peptide, protoxin-I, as the first high-affinity peptide antagonist of the transient receptor potential ankyrin 1 (TRPA1) channel. Nitabach’s team also used toxineering to create a novel protoxin-I mutant with improved specificity for TRPA1, underscoring the value of the approach for pharmaceutical discovery." https://lnkd.in/eQA7Yck View in LinkedIn

"ACTIVATION in temperature-sensitive TRP channels is characterized by very large enthalpy changes that are compensated by similarly large entropy changes. For example, enthalpy changes of about 100 kcal/mol, 200 kcal/mol, and 60 kcal/mol are involved in the opening of TRPV1, TRPV2, and TRPM8, respectively." https://lnkd.in/eZQCjnY View in LinkedIn

VENOM PAYLOAD. "A key issue in ion channel toxin biology has been the mining of this great pharmacological diversity—e.g., spiders alone are estimated to collectively contain millions of distinct peptide toxins in their venoms —to identify toxins with high affinity for particular ion channel targets." https://lnkd.in/ecaVp5Q View in LinkedIn

CENTER OF SYMMETRY PATHWAY. "ThermoTRPs share a common organization. They are tetramers where the permeation pathway is located in the center of symmetry of the channel. ThermoTRP are activated by different agonist obtained from different plants." https://lnkd.in/eZQCjnY View in LinkedIn

VENOM ANTAGONISTS. "The venoms of predators, such as spiders, scorpions, cone snails, sea anemones, and snakes, have been an excellent source of peptide diversity for drug discovery and as pharmacological tools for elucidating the structure, function, and physiological properties of ion channels." https://lnkd.in/ecaVp5Q View in LinkedIn

ANTAGONISTS. "The importance of TRPA1 in pain signaling makes it a potential target for the treatment of pathological pain. While some small-molecule TRPA1 antagonists have been identified, no peptide antagonists of TRPA1 have been reported." https://lnkd.in/ecaVp5Q View in LinkedIn

BLOCKING TRPA1. "Genetic deletion or pharmacological blockade of TRPA1 produces inhibitory activity in mouse models of anxiety and depression. These results imply that TRPA1 exerts tonic control, promoting anxiety and depression, and that TRPA1 antagonism has potential as an innovative strategy for the treatment of anxiety and mood disorders." https://lnkd.in/e-Efbhd View in LinkedIn

PSYCHIATRIC LINK. "Transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) are involved in many biological processes, including nociception and hyperalgesia. Whereas the involvement of TRPV1 in psychiatric disorders such as anxiety and depression has been reported, little is known regarding the role of TRPA1 in these conditions." https://lnkd.in/e-Efbhd View in LinkedIn