Are therapeutic effects of antiacne agents mediated by activation of FoxO1 and inhibition of mTORC1?
| Autor: | Gerd Schmitz, Bodo C. Melnik |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
mTORC1 inhibitors Retinoic acid Hypothesis Letter FOXO1 Dermatology mTORC1 Biology Pharmacology AMP-Activated Protein Kinases Mechanistic Target of Rapamycin Complex 1 Biochemistry antiacne drugs chemistry.chemical_compound Enzyme activator AMP-activated protein kinase Internal medicine Acne Vulgaris medicine Humans Dicarboxylic Acids Isotretinoin Molecular Biology Protein kinase B acne Benzoyl Peroxide Kinase Forkhead Box Protein O1 TOR Serine-Threonine Kinases AMPK Forkhead Transcription Factors Tetracycline Erythromycin Up-Regulation Enzyme Activation Oxidative Stress Endocrinology chemistry Multiprotein Complexes FoxOs biology.protein Dermatologic Agents biological phenomena cell phenomena and immunity hormones hormone substitutes and hormone antagonists |
| Zdroj: | Experimental Dermatology |
| ISSN: | 1600-0625 0906-6705 |
| Popis: | Acne pathogenesis has recently been linked to decreased nuclear FoxO1 levels and increased mTORC1 activity. This hypothesis postulates that antiacne agents either enhance nuclear FoxO activity or inhibit mTORC1. Benzoyl peroxide (BPO), by activation of oxidative stress-inducible kinases, increases nuclear FoxO levels promoting Sestrin3-mediated AMPK activation. Furthermore, BPO-derived ROS may activate AMPK via ataxia–telangiectasia mutated. Isotretinoin and all-trans retinoic acid may stimulate FoxO gene expression. Doxycycline may enhance FoxOs nuclear retention by inhibiting the expression of exportin 1. Suppression of TNFα signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKβ-TSC1-mediated mTORC1 activation. Erythromycin attenuates ERK1/2 activity and thereby increases TSC2. Azelaic acid may decrease mTORC1 by inhibiting mitochondrial respiration, increasing cellular ROS and nuclear FoxO levels. Antiandrogens may attenuate mTORC1 by suppressing mTORC2-mediated Akt/TSC2 signalling. This hypothesis unmasks a common mode of action of antiacne agents as either FoxO enhancers or mTORC1 inhibitors and thus provides a rational approach for the development of new antiacne agents. |
| Databáze: | OpenAIRE |
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