Papers of the Week

Transient receptor potential melastatin 2 (TRPM2) is a sub family of TRP channels which plays a central role in producing neuro pathophysiological diseases such as Alzheimer's, Parkinson's and other neuropathic pain which are major health concern worldwide. However, their pharmacological pathway has not been fully characterized which is a significant gap in our knowledge. TRPM2 is mainly expressed in brain, bone merrow, endocrine and endothelia cells. Under oxidative stress, TRPM2 increases intracellular Ca ions due to protein oxidation that causes several neurological disorders. Reactive oxygen species (ROS) production and oxidative stress are the primary cause of many pathological disease processes. Natural compounds with medicinal properties are useful and effective source for the treatment of various diseases since ancient times. Caffeic acid and its analogs, such as caffeic, chlorogenic, salvianolic A & B, and rosmarinic acid have anti-inflammatory, antimicrobial, antioxidant, anesthetic, and cytotoxic properties. There is a critical need for new drug planning that focuses on oxidative interaction in targeted TRPM2 ion channels and intracellular ion signaling, which will regulate neuropathological diseases by interacting other TRP channels. Our ongoing experiment demonstrate that increase in ROS was decreased by caffeic acid analogs salvianolic, and rosmarinic acid more than caffeic and chlorogenic acid which was reflected by GST inhibition activity assay. Our experiments also evaluate the analgesic effects of caffeic acid analogs on TRPM2 channel by measuring intracellular calcium. Therefore, this pilot project aims to identify caffeic acid analogs as lead compounds that target TRPM2 which is one of the key pathway players for controlling various neurodegenerative diseases.