Photopharmacology: using light to control cold sensors

Located in the cell membrane, TRPM8 ion channels are known as receptors that recognize cold and respond to menthol, the cooling agent in peppermint. In addition, these channels influence pain perception and play a key role in numerous diseases. This makes them promising targets for the development of new drugs to combat cancer, metabolic diseases, inflammations, and more.

Researchers have been studying TRPM8 ion channels in order to better understand their complex functions and develop innovative therapeutic approaches. An LMU research team led by Professor Michael Mederos y Schnitzler (Walther Straub Institute of Pharmacology and Toxicology) and Dr. David B. Konrad, in collaboration with Professor Dirk Trauner (University of Pennsylvania) and Professor Ursula Storch (University of Regensburg), has now made an important breakthrough in this area. The researchers have developed an innovative molecule called azo-menthol, which is able to precisely control TRPM8 channels using light, as they report in the journal Angewandte Chemie.

“With azo-menthol, it’s possible for the first time to specifically activate TRPM8 channels using UV light and deactivate them again with blue light – and to do so in a way that’s spatiotemporally precise and reversible,” emphasizes Mederos y Schnitzler. Using light as a tool to control biological processes has great therapeutic potential, say the authors. “Such photopharmacological approaches could help, for example, avoid systemic side effects such as arise during conventional chemotherapy,” notes Mederos y Schnitzler. “Accordingly, the progress being made in this area opens up exciting new prospects for the development of novel therapies that could be more precise in their action and gentler in their effects.”

„Mit Azo-Menthol ist es erstmals möglich, TRPM8-Kanäle mithilfe von UV-Licht gezielt zu aktivieren und mit Blaulicht wieder zu deaktivieren – und das zeitlich und örtlich präzise sowie reversibel“, betont Mederos y Schnitzler. Licht als Werkzeug zur Steuerung von biologischen Prozessen zu nutzen, hat großes therapeutisches Potenzial, so die Autoren. „Solche photopharmakologischen Ansätze könnten beispielsweise helfen, systemische Nebenwirkungen, wie sie etwa bei einer konventionellen Chemotherapie auftreten, zu vermeiden“, sagt Mederos y Schnitzler. „Daher eröffnen die Fortschritte auf diesem Gebiet spannende Perspektiven für die Entwicklung neuartiger Therapien, die präziser und schonender wirken könnten.“

Jasmin Becker et al.: Optical Control of TRPM8 Channels with Photoswitchable Menthol. Angewandte Chemie 2024