Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage.
Photoaging and photocarcinogenesis are the two Janus faces of skin photodamage. Reactivity-based design of prototype agents that antagonize, modulate and reverse the chemistry of skin photodamage holds promise in delivering unprecedented therapeutic benefit. In contrast to structure-based approaches that use selective ligands to target macromolecules, reactivity-based drug discovery uses chemical reagents as therapeutics to target reactive chemical species as key mediators of skin photo-oxidative stress. The following classes of reactivity-based agents for skin photoprotection can be distinguished based on their mechanism of action: direct antagonists of photo-oxidative stress (sunscreens, quenchers of photo-excited states, antioxidants, redox modulators and glycation inhibitors) and skin photo-adaptation inducers (nuclear factor erythroid 2-related factor 2 [Nrf2] activators, heat-shock response inducers and metallothionein inducers).
Wondrak
Georg T
GT
Arizona Cancer Center, University of Arizona, Department of Pharmacology and Toxicology, College of Pharmacy, 1515 North Campbell Avenue, Tucson, AZ 85724, USA. wondrak@pharmacy.arizona.edu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D008668:Metallothionein / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000517:prevention & control*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010777:Photochemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D013471:Sunburn / Q000378:metabolism / Q000517:prevention & control*; D013473:Sunscreening Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014466:Ultraviolet Rays; D015854:Up-Regulation
D000975:Antioxidants; D002614:Chelating Agents; D017127:Glycation End Products, Advanced; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D013473:Sunscreening Agents; D008668:Metallothionein