Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond?

Bioessays. 2017 Jul 7. doi: 10.1002/bies.201700029. [Epub ahead of print]

Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond?

Laura Jadkauskaite1), Pierre A. Coulombe2), Matthias Sch€afer3), Albena T. Dinkova-Kostova4), Ralf Paus1)5)and Iain S. Haslam1)6)

Widespread expression of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide-induced hair growth inhibition. Multiple parameters can increasethe levels of reactive oxygen species in the HF, for example melanogenesis, depilation-induced trauma, neurogenic and autoimmune inflammation, toxic drugs, environmental stressors such as UV irradiation, genetic defects and aging-associated mitochondrial dysfunction. In this re-view, the potential mechanisms whereby NRF2 activation could prove beneficial in treatment of redox-associated HF disorders are therefore discussed. Introduction Cutaneous oxidative stress management: An emerging role for NRF2 Few, if any organs are as exposed to as vast an array of external stressors as the skin; contact with the commensal microbiota, bacterial, viral and fungal pathogens, UV radiation (UVR), heat, cold, dryness, humidity and phytotox-ins have all contributed to shape the anatomic and functional characteristics of mammalian skin during evolution. When confounded by internal stressors, such as metabolic stress(e.g. in diabetes mellitus) or psycho-emotional stress leading to neurogenic skin inflammation, a common consequence is oxidative imbalance [1, 2]. The resulting DNA damage, lipid peroxidation and enzyme inactivation can lead to cellular toxicity and disease pathogenesis [3].Skin appendages, n otably hair f ollicles (HFs), can also beexpos ed to h igh leve ls of reactive oxygen species (ROS),which are generated through metaboli c reactions occurringmostly in the mitochondria, peroxisomes and the endoplasmic reticulum (ER) as well as in the plasma membrane [4, 5].Indeed, numerous intracellular and trans-membrane enzymes, including xanthine oxidase, cytochrome P450s and NADPH oxidase produce ROS as metabolic by-products [6, 7]. Despite their involvement in redox stress.

Keywords:.alopecia; chemotherapy and hair follicle; hair graying; inflammation; NRF2; oxidative stress