Alopecia Areata: A Review of the Role of Oxidative Stress, Possible Biomarkers, and Potential Novel Therapeutic Approaches

Abstract

Alopecia areata (AA) is a dermatological condition characterized by non-scarring hair loss. Exact etiopathogenesis of AA is still unknown although it is known that several factors contribute to the collapse of the hair-follicle (HF)-immune-privileged (IP) site. Oxidative stress (OS) plays an important role in skin diseases. The aim of this review was to clarify the role of OS in AA pathogenesis and diagnosis, and to discuss potential treatment options. Oxidative-stress markers are altered in serum and skin samples of patients with AA, confirming a general pro-oxidative status in patients with AA. OS induces MHC class I chain-related A (MICA) expression in HF keratinocytes that activates the receptor NKG2D, expressed in NK cells and CD8+ T cytotoxic cells leading to destabilization of the HF immune-privileged site through the production of IFN-γ that stimulates JAK1 and JAK2 pathways. OS also activates the KEAP1-NRF2 pathway, an antioxidant system that contributes to skin homeostasis. In addition, a decrease of ATG5 and LC3B in the hair matrix and an increase in p62 levels indicates a reduction of intrafollicular autophagy during the evolution of AA. Potential biomarkers of OS in AA could be: malondialdehyde (MDA), advanced glycation end-products (AGEs), and ischemic-modified albumin (IMA). JAK inhibitors are the new frontier in treatment of AA and the use of nutraceuticals that modulate the OS balance, in combination with standard treatments, represent promising therapeutic tools.

TRPM2‐dependent autophagy inhibition exacerbates oxidative stress‐induced CXCL16 secretion by keratinocytes in vitiligo

“…Furthermore, decreased Atg5 also leads to NF‐κB activation after renal injury, IL‐1β production under liver injury, and an enhanced CD8 + T cell response in antiviral immunity [64–66], suggesting autophagic protein Atg5 also limits immunity in other noxious conditions. Interestingly, Atg5 reduction was also found in the hair matrix of alopecia areata lesions, which indicates an intrafollicular autophagy inhibition during alopecia areata evolution [67]. To conclude, Atg5 has emerged as a crucial spotlight in autophagy suppression that drives the development of autoimmune skin diseases.…”

Spore Oil-Functionalized Selenium Nanoparticles Protect Pancreatic Beta Cells from Palmitic Acid-Induced Apoptosis via Inhibition of Oxidative Stress-Mediated Apoptotic Pathways

“…Catalytic reduction of glutathione disulfide (GSSG) to GSH is one of the key enzymes in the glutathione redox cycle [ 53 ]. Under the action of PA, the activity of antioxidant enzymes in pancreatic β-cells is greatly affected, and MDA, the final product of lipid peroxidation, is produced in large quantities, which leads to the weakening of the free-radical-scavenging ability of β-cells and then apoptosis [ 54 ]. In the present study, the contents of SOD, GSH, GPX, CAT, and TrxR in cells were detected, which demonstrated that PA significantly inhibited the activity of antioxidant enzymes in cells, induced the production of a large amount of MDA, and increased the degree of lipid peroxidation in the body, thus leading to cell damage ( Figure 6 A–H).…”

Role of neurogenic inflammation in the pathogenesis of alopecia areata

“…

Alopecia areata (AA) represents a form of hair loss characterized by scarless alopecia, most commonly smooth, round, well-defined patches that completely fall off, appear suddenly, and last for weeks. 1 It is an autoimmune and inflammatory illness primarily driven by T cells. 2 In more severe instances, alopecia may affect the entire scalp or body, known as alopecia totalis (AT) or alopecia universalis (AU).

…”