Abstract
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).
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Antioxidants / pharmacology
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Antioxidants / therapeutic use*
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Chelating Agents / pharmacology
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Chelating Agents / therapeutic use*
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Drug Design
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Glycation End Products, Advanced / metabolism
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Glycosylation / drug effects
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Heat-Shock Response / drug effects
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Humans
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Metallothionein / metabolism
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NF-E2-Related Factor 2 / metabolism
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Neoplasms, Radiation-Induced / metabolism
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Neoplasms, Radiation-Induced / prevention & control*
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Oxidation-Reduction
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Oxidative Stress / drug effects
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Photochemistry
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects
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Skin / drug effects*
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Skin / metabolism
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Skin / radiation effects
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Skin Aging / drug effects
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Skin Aging / radiation effects
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Skin Neoplasms / metabolism
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Skin Neoplasms / prevention & control*
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Sunburn / metabolism
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Sunburn / prevention & control*
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Sunscreening Agents / pharmacology
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Sunscreening Agents / therapeutic use*
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Ultraviolet Rays*
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Up-Regulation
Substances
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Antioxidants
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Chelating Agents
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Glycation End Products, Advanced
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NF-E2-Related Factor 2
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Reactive Oxygen Species
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Sunscreening Agents
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Metallothionein