Double-edged sword effect of GPX4 in skin homeostasis and diseases
Hanzhang Xu1, Li Yang1, Yingli Wu1,2
1Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Glutathione peroxidase 4 (GPX4) is a crucial antioxidant enzyme that plays a vital role in protecting cells from oxidative damage and lipid peroxidation. In the context of skin diseases, GPX4 serves as a key regulator of oxidative stress and inflammation, both of which are significant features of various skin conditions. By preventing lipid peroxidation and maintaining membrane integrity, GPX4 acts as a safeguard against cell death pathways, particularly ferroptosis, in skin diseases. Dysregulation of GPX4 in conditions such as dermatitis, psoriasis, and skin cancer is linked to heightened oxidative stress, inflammation, and tissue damage. Understanding the role of GPX4 and its intricate interactions in skin disease pathogenesis can aid in more effectively targeting oxidative stress and inflammation, leading to promising therapeutic interventions. This review summarizes the role of GPX4 in maintaining skin homeostasis and its involvement in disease, proposing strategies to target GPX4, including its post-translational modifications. Investigate the precise mechanism through which GPX4 influences the onset of skin diseases, and utilize GPX4 agonists or inhibitors as potential treatments.
Insights
Glutathione peroxidase 4 (GPX4) protects skin cells from oxidative damage and ferroptosis. Targeting GPX4 offers new therapeutic strategies for skin diseases like dermatitis, psoriasis, and cancer.
Area of Science:
- Biochemistry
- Dermatology
- Cell Biology
Background:
- Glutathione peroxidase 4 (GPX4) is a key antioxidant enzyme.
- GPX4 prevents lipid peroxidation and maintains cell membrane integrity.
- Oxidative stress and inflammation are hallmarks of many skin diseases.
Purpose of the Study:
- To review the role of GPX4 in skin homeostasis and disease.
- To explore GPX4's involvement in skin disease pathogenesis.
- To propose therapeutic strategies targeting GPX4.
Main Methods:
- Literature review of GPX4's function in skin.
- Analysis of GPX4's role in oxidative stress and ferroptosis.
- Investigation of GPX4 dysregulation in skin conditions.
Main Results:
- GPX4 dysregulation is linked to increased oxidative stress, inflammation, and tissue damage in skin diseases.
- GPX4 prevents ferroptosis, a cell death pathway implicated in skin pathologies.
- GPX4's function is critical for maintaining skin homeostasis.
Conclusions:
- GPX4 is a vital regulator of skin health and disease.
- Targeting GPX4, including its post-translational modifications, presents promising therapeutic avenues.
- Further research into GPX4 mechanisms can lead to novel treatments for skin diseases.
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