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. 2016 Sep 15;7:12840. doi: 10.1038/ncomms12840

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Copyright © 2016, The Author(s)

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(a) Cold triggers ROS generation, but cold is insufficient to activate TRPA1 with conserved PHD-mediated hydroxylation of a proline residue. (b) Inhibition of PHD (or mutating the proline residue to alanine) enhances the sensitivity of TRPA1 to ROS. This enhanced sensitivity enables TRPA1 to sense cold-evoked ROS, which causes cold hypersensitivity. The dotted arrows indicate the indirect or multiple pathway.