Abstract
Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of pigmentation. Among various hypotheses proposed for the pathogenesis of vitiligo, oxidative stress-induced immune response that ultimately leads to melanocyte death remains most widely accepted. Oxidative stress which causes elevated levels of reactive oxygen species (ROS) can lead to dysfunction of molecules and organelles, triggering further immune response, and ultimately melanocyte death. In recent years, a variety of cell death modes have been studied, including apoptosis, autophagy and autophagic cell death, ferroptosis, and other novel modes of death, which will be discussed in this review in detail. Oxidative stress is also strongly linked to these modes of death. Under oxidative stress, ROS could induce autophagy by activating the Nrf2 antioxidant pathway of melanocytes. However, persistent stimulation of ROS might eventually lead to excessive activation of Nrf2 antioxidant pathway, which in turn will inactivate autophagy. Moreover, ferroptosis may be triggered by oxidative-related transcriptional production, including ARE, the positive feedback loop related to p62, and the reduced activity and expression of GPX4. Therefore, it is reasonable to infer that these modes of death are involved in the oxidative stress response, and that oxidative stress also acts as an initiator for various modes of death through some complex mechanisms. In this study, we aim to summarize the role of oxidative stress in vitiligo and discuss the corresponding mechanisms of interaction between various modes of cell death and oxidative stress. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of vitiligo.
Highlights
Vitiligo is an acquired pigmentation disorder of unknown origin and the most frequent cause of depigmentation, causing an estimated prevalence between 0.5 and 2% worldwide [1]
There have been various modes of cell death, and apoptosis has been considered the main mode of melanocyte death in vitiligo, we mainly discuss autophagy and ferroptosis in vitiligo that is closely related to oxidative stress
Since autophagy possesses a protective and restorative function to the damage induced by oxidative stress, deficiency of autophagy might lead to alteration of cell functions, especially on reactive oxygen species (ROS) scavenging
Summary
Vitiligo is an acquired pigmentation disorder of unknown origin and the most frequent cause of depigmentation, causing an estimated prevalence between 0.5 and 2% worldwide [1]. Numerous studies have attempted to illustrate the pathogenesis behind vitiligo, including the degenerative theory, genetic factors, oxidative stress, autoimmune hypothesis, and cell detachment mechanisms. Several researchers have evaluated the influence of alopecia areata and/or autoimmune thyroid disease on vitiligo by using the biomarkers [3, 4]. Even fibroblast has proved to play an essential role in the pathogenesis of vitiligo [5]. These theories are insufficient to explain the pathogenesis of vitiligo individually, and the contribution of each hypothesis is still under debate [6,7,8]. The oxidative stress hypothesis showed that reactive oxygen species (ROS) are induced by multiple factors and impair antioxidant defenses, breaking the melanocyte redox homeostasis, which may contribute to the onset of vitiligo. This review provides new insight for the investigation of the potentially broad application of the cellular cross-talk in vitiligo
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