Dysfunction of Autophagy: A Possible Mechanism Involved in the Pathogenesis of Vitiligo by Breaking the Redox Balance of Melanocytes

Abstract

Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of functional melanocytes from the epidermis and follicular reservoir. Among multiple hypotheses which have been proposed in the pathogenesis of vitiligo, autoimmunity and oxidative stress-mediated toxicity in melanocytes remain most widely accepted. Macroautophagy is a lysosome-dependent degradation pathway which widely exists in eukaryotic cells. Autophagy participates in the oxidative stress response in many cells, which plays a protective role in preventing damage caused by oxidative stress. Recent studies have enrolled autophagy as an important regulator in limiting damage caused by UV light and lipid oxidation, keeping oxidative stress in a steady state in epidermal keratinocytes and maintaining normal proliferation and aging of melanocytes. Impairment of autophagy might disrupt the antioxidant defense system which renders melanocytes to oxidative insults. These findings provide supportive evidence to explore new ideas of the pathogenesis of vitiligo and other pigmentation disorders.

Evaluation of Annexin A1 Protein in an Infectious Keratitis Model: Therapeutic Perspectives

“…Studies of the host's immune response against P. aeruginosa show that the condition and development of the disease is not only related to the production of exoenzymes and other byproducts released from the bacterial proliferation [7,8] but the production of cytokines, some eicosanoids and other molecular mediators of the host are also involved in ulceration and angiogenesis, contributing to stromal necrosis and corneal edema, during bacterial keratitis [9]. Thus, infectious ocular diseases not only involve the effects of colonization factors and bacterial virulence, but also the immune response of the host to the pathogen [10].…”

Computational Study of C-X-C Chemokine Receptor (CXCR)3 Binding with Its Natural Agonists Chemokine (C-X-C Motif) Ligand (CXCL)9, 10 and 11 and with Synthetic Antagonists: Insights of Receptor Activation towards Drug Design for Vitiligo

“…Vitiligo is a hypopigmentary skin autoimmune pathology characterized by the development of lesions lacking melanin, which is the natural pigment of the skin produced by melanocytes. Vitiligo affects 0.5–2% of the global population, with the highest incidence rates occurring in India, Japan, and Mexico [ 1 , 2 , 3 ]. This pathology can be classified as either nonsegmental, due to the symmetrical arrangement of the lesions, or segmental, due to the nonsymmetrical disposition of the lesions [ 4 ].…”

“…The etiology of vitiligo is not completely understood; nevertheless, different theories could explain the development and progression of this pathology. Amongst these, oxidative stress and the involvement of the immune system are positioned as the most accepted theories, in addition to genetic factors that predispose individuals to vitiligo [ 3 , 12 , 13 ]. An increase in reactive oxygen species that cause DNA damage, the release of exosomes with intracellular peptides and misfolded proteins, and apoptosis have been reported.…”

“…An increase in reactive oxygen species that cause DNA damage, the release of exosomes with intracellular peptides and misfolded proteins, and apoptosis have been reported. Thus, released peptides and misfolded proteins can be recognized by the immune system and stimulate the development of autoreactive lymphocytes responsive to melanocyte epitopes [ 3 , 14 , 15 ]. Moreover, CD8 + T lymphocytes were identified as being responsible for the progress and intensity of vitiligo; once melanocyte antigens are recognized, these lymphocytes release granzyme and perforin, promoting apoptosis in melanocyte cells.…”

Sodium tanshinone IIA silate increases melanin synthesis by activating the MAPK and PKA pathways and protects melanocytes from H2O2-induced oxidative stress

“…The melanocytes of vitiligo are particularly vulnerable to damage or apoptosis under certain circumstances such as excessive ROS production. 8,9 ROS can attack melanocytes and interfere with the normal metabolism, proliferation, and differentiation of melanocytes, causing cell apoptosis and defects. 10 Excessive accumulation of ROS in the epidermis of vitiligo patients leads to the disorders of melanocytes, resulting in damage to the mitochondrial electron transport chain; this further forms a vicious cycle and leads to the destruction of melanocytes.…”